Abstract
Three major approaches of cancer therapy can be enunciated as delivery of biotherapeutics, tumor image analysis, and immunotherapy. Liposomes, artificial fat bubbles, are long known for their capacity to encapsulate a diverse range of bioactive molecules and release the payload in a sustained, stimuli-responsive manner. They have already been widely explored as a delivery vehicle for therapeutic drugs as well as imaging agents. They are also extensively being used in cancer immunotherapy. On the other hand, exosomes are naturally occurring nanosized extracellular vesicles that serve an important role in cell–cell communication. Importantly, the exosomes also have proven their capability to carry an array of active pharmaceuticals and diagnostic molecules to the tumor cells. Exosomes, being enriched with tumor antigens, have numerous immunomodulatory effects. Much to our intrigue, in recent times, efforts have been directed toward developing smart, bioengineered, exosome-liposome hybrid nanovesicles, which are augmented by the benefits of both vesicular systems. This review attempts to summarize the contemporary developments in the use of exosome and liposome toward cancer diagnosis, therapy, as a vehicle for drug delivery, diagnostic carrier for tumor imaging, and cancer immunotherapy. We shall also briefly reflect upon the recent advancements of the exosome-liposome hybrids in cancer therapy. Finally, we put forward future directions for the use of exosome/liposome and/or hybrid nanocarriers for accurate diagnosis and personalized therapies for cancers.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Sinha D, Roy S, Saha P, Chatterjee N, Bishayee A. Trends in research on exosomes in cancer progression and anticancer therapy. Cancers. 2021;13:326.
Zhang Y, Liu Y, Liu H, Tang WH. Exosomes: biogenesis, biologic function and clinical potential. Cell Biosci. 2019;9:19.
Dai J, Su Y, Zhong S, Cong L, Liu B, Yang J, et al. Exosomes: key players in cancer and potential therapeutic strategy. Signal Transduct Target Ther. 2020;5:145.
Modani S, Tomar D, Tangirala S, Sriram A, Mehra NK, Kumar R, et al. An updated review on exosomes: biosynthesis to clinical applications. J Drug Target. 2021;29:925–40.
De Leo V, Milano F, Agostiano A, Catucci L. Recent advancements in polymer/liposome assembly for drug delivery: from surface modifications to hybrid vesicles. Polymers. 2021;13:1027.
Barenholz Y. Doxil®—the first FDA-approved nano-drug: lessons learned. J Control Release. 2012;160:117–34.
Petersen GH, Alzghari SK, Chee W, Sankari SS, La-Beck NM. Meta-analysis of clinical and preclinical studies comparing the anticancer efficacy of liposomal versus conventional non-liposomal doxorubicin. J Control Release. 2016;232:255–64.
Chen EC, Fathi AT, Brunner AM. Reformulating acute myeloid leukemia: liposomal cytarabine and daunorubicin (CPX-351) as an emerging therapy for secondary AML. Onco Targets Ther. 2018;11:3425–34.
Olusanya T, Haj Ahmad R, Ibegbu D, Smith J, Elkordy A. Liposomal drug delivery systems and anticancer drugs. Molecules. 2018;23:907.
Harding CV, Heuser JE, Stahl PD. Exosomes: looking back three decades and into the future. J Cell Biol. 2013;200:367–71.
Tschuschke M, Kocherova I, Bryja A, Mozdziak P, Angelova Volponi A, Janowicz K, et al. Inclusion biogenesis, methods of isolation and clinical application of human cellular exosomes. J Clin Med. 2020;9:436.
Mathivanan S, Fahner CJ, Reid GE, Simpson RJ. ExoCarta 2012: database of exosomal proteins, RNA and lipids. Nucleic Acids Res. 2012;40:D1241–4.
Shimaoka M, Kawamoto E, Gaowa A, Okamoto T, Park E. Connexins and integrins in exosomes. Cancers. 2019;11:106.
McAndrews KM, Kalluri R. Mechanisms associated with biogenesis of exosomes in cancer. Mol Cancer. 2019;18:52.
Yu X, Harris SL, Levine AJ. The regulation of exosome secretion: a novel function of the p53 protein. Cancer Res. 2006;66:4795–801.
Khan YY, Suvarna V. Liposomes containing phytochemicals for cancer treatment—an Update. Int J Curr Pharm Res. 2016;9:20–4.
Mukherjee A, Paul M, Mukherjee S. Recent progress in the theranostics application of nanomedicine in lung cancer. Cancers. 2019;11:597.
Sercombe L, Veerati T, Moheimani F, Wu SY, Sood AK, Hua S. Advances and challenges of liposome assisted drug delivery. Front Pharmacol. 2015;6:286.
Agrawal V, Paul MK, Mukhopadhyay AK. 6-mercaptopurine and daunorubicin double drug liposomes—preparation, drug-drug interaction and characterization. J Liposome Res. 2008;15:141–55.
Abraham SA, Waterhouse DN, Mayer LD, Cullis PR, Madden TD, Bally MB. The liposomal formulation of doxorubicin. Methods Enzymol. 2005;391:71–97.
Gu Z, Da Silva C, Van der Maaden K, Ossendorp F, Cruz L. Liposome-based drug delivery systems in cancer immunotherapy. Pharmaceutics. 2020;12:1054.
Elkhoury K, Koçak P, Kang A, Arab-Tehrany E, Ellis Ward J, Shin SR. Engineering smart targeting nanovesicles and their combination with hydrogels for controlled drug delivery. Pharmaceutics. 2020;12:849.
Torchilin VP. Micellar nanocarriers: pharmaceutical perspectives. Pharmacol Res. 2006;24:1–16.
Mukherjee A, Waters AK, Kalyan P, Achrol AS, Kesari S, Yenugonda VM. Lipid-polymer hybrid nanoparticles as a next-generation drug delivery platform: state of the art, emerging technologies, and perspectives. Int J Nanomed. 2019;14:1937–52.
Ahn HK, Jung M, Sym SJ, Shin DB, Kang SM, Kyung SY, et al. A phase II trial of Cremorphor EL-free paclitaxel (Genexol-PM) and gemcitabine in patients with advanced non-small cell lung cancer. Cancer Chemother Pharmacol. 2014;74:277–82.
Johnsson M, Edwards K. Liposomes, disks, and spherical micelles: aggregate structure in mixtures of gel phase phosphatidylcholines and poly(ethylene glycol)-phospholipids. Biophys J. 2003;85:3839–47.
Srivastava A, Amreddy N, Babu A, Panneerselvam J, Mehta M, Muralidharan R, et al. Nanosomes carrying doxorubicin exhibit potent anticancer activity against human lung cancer cells. Sci Rep. 2016;6:38541.
Mansouri K, Rasoulpoor S, Daneshkhah A, Abolfathi S, Salari N, Mohammadi M, et al. Clinical effects of curcumin in enhancing cancer therapy: a systematic review. BMC Cancer. 2020;20:791.
Sun D, Zhuang X, Xiang X, Liu Y, Zhang S, Liu C, et al. A novel nanoparticle drug delivery system: the anti-inflammatory activity of curcumin is enhanced when encapsulated in exosomes. Mol Ther. 2010;18:1606–14.
Yang T, Martin P, Fogarty B, Brown A, Schurman K, Phipps R, et al. Exosome delivered anticancer drugs across the blood-brain barrier for brain cancer therapy in Danio Rerio. Pharmacol Res. 2015;32:2003–14.
Tian Y, Li S, Song J, Ji T, Zhu M, Anderson GJ, et al. A doxorubicin delivery platform using engineered natural membrane vesicle exosomes for targeted tumor therapy. Biomaterials. 2014;35:2383–90.
McAndrews KM, Che SPY, LeBleu VS, Kalluri R. Effective delivery of STING agonist using exosomes suppresses tumor growth and enhances antitumor immunity. J Biol Chem. 2021;296:100523.
Koh E, Lee EJ, Nam G-H, Hong Y, Cho E, Yang Y, et al. Exosome-SIRPα, a CD47 blockade increases cancer cell phagocytosis. Biomaterials. 2017;121:121–9.
Davis ME, Zuckerman JE, Choi CHJ, Seligson D, Tolcher A, Alabi CA, et al. Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles. Nature. 2010;464:1067–70.
Kaczmarek JC, Kowalski PS, Anderson DG. Advances in the delivery of RNA therapeutics: from concept to clinical reality. Genome Med. 2017;9:60.
Kristen AV, Ajroud-Driss S, Conceição I, Gorevic P, Kyriakides T. Obici L. Patisiran, an RNAi therapeutic for the treatment of hereditary transthyretin-mediated amyloidosis. Neurodegener Dis Manag. 2019;9:5–23.
O’Brien K, Breyne K, Ughetto S, Laurent LC, Breakefield XO. RNA delivery by extracellular vesicles in mammalian cells and its applications. Nat Rev Mol Cell Biol. 2020;21:585–606.
Alvarez-Erviti L, Seow Y, Yin H, Betts C, Lakhal S, Wood MJA. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol. 2011;29:341–5.
He J, Banizs A, Huang T, Dryden K, Berr S, Stone J, et al. In vitro evaluation of endothelial exosomes as carriers for small interfering ribonucleic acid delivery. Int J Nanomed. 2014;9:4223–30.
Wahlgren J, Karlson TDL, Brisslert M, Vaziri Sani F, Telemo E, Sunnerhagen P, et al. Plasma exosomes can deliver exogenous short interfering RNA to monocytes and lymphocytes. Nucleic Acids Res. 2012;40:e130–e.
Shtam TA, Kovalev RA, Varfolomeeva E, Makarov EM, Kil YV, Filatov MV. Exosomes are natural carriers of exogenous siRNA to human cells in vitro. Cell Commun Signal. 2013;11:88.
Ohno S-i, Takanashi M, Sudo K, Ueda S, Ishikawa A, Matsuyama N, et al. Systemically injected exosomes targeted to EGFR deliver antitumor microRNA to breast cancer cells. Mol Ther. 2013;21:185–91.
Pattni BS, Chupin VV, Torchilin VP. New developments in liposomal drug delivery. Chem Rev. 2015;115:10938–66.
Mukherjee A, Madamsetty VS, Paul MK, Mukherjee S. Recent advancements of nanomedicine towards antiangiogenic therapy in cancer. Int J Mol Sci. 2020;21:455.
Bulbake U, Doppalapudi S, Kommineni N, Khan W. Liposomal formulations in clinical use: an updated review. Pharmaceutics. 2017;9:12.
Din FU, Aman W, Ullah I, Qureshi OS, Mustapha O, Shafique S, et al. Effective use of nanocarriers as drug delivery systems for the treatment of selected tumors. Int J Nanomed. 2017;12:7291–309.
Patra JK, Das G, Fraceto LF, Campos EVR. Rodriguez-Torres MdP, Acosta-Torres LS, et al. Nano based drug delivery systems: recent developments and future prospects. J Nanobiotechnol. 2018;16:71.
Akinc A, Maier MA, Manoharan M, Fitzgerald K, Jayaraman M, Barros S, et al. The Onpattro story and the clinical translation of nanomedicines containing nucleic acid-based drugs. Nat Nanotechnol. 2019;14:1084–7.
Melo SA, Luecke LB, Kahlert C, Fernandez AF, Gammon ST, Kaye J, et al. Glypican-1 identifies cancer exosomes and detects early pancreatic cancer. Nature. 2015;523:177–82.
Chuo ST-Y, Chien JC-Y, Lai CP-K. Imaging extracellular vesicles: current and emerging methods. J Biomed Sci. 2018;25:91.
Lai CP, Tannous BA, Breakefield XO. Noninvasive in vivo monitoring of extracellular vesicles. Biolumin Imaging. 2014;19:249–58.
Zhang C, Yan Y, Zou Q, Chen J, Li C. Superparamagnetic iron oxide nanoparticles for MR imaging of pancreatic cancer: potential for early diagnosis through targeted strategies. Asia Pac J Clin Oncol. 2016;12:13–21.
Hu L, Wickline SA, Hood JL. Magnetic resonance imaging of melanoma exosomes in lymph nodes. Magn Reson Med. 2015;74:266–71.
Marzola P, Busato A, Bonafede R, Bontempi P, Scambi I, Schiaffino L, et al. Magnetic resonance imaging of ultrasmall superparamagnetic iron oxide-labeled exosomes from stem cells: a new method to obtain labeled exosomes. Int J Nanomed. 2016;11:2481–90.
Hwang DW, Choi H, Jang SC, Yoo MY, Park JY, Choi NE, et al. Noninvasive imaging of radiolabeled exosome-mimetic nanovesicle using 99mTc-HMPAO. Sci Rep. 2015;5:15636.
Betzer O, Perets N, Angel A, Motiei M, Sadan T, Yadid G, et al. In vivo neuroimaging of exosomes using gold nanoparticles. ACS Nano. 2017;11:10883–93.
Smania MA. Liquid biopsy for cancer screening, diagnosis, and treatment. J Am Assoc Nurse Pract. 2020;32:5–7.
Ignatiadis M, Sledge GW, Jeffrey SS. Liquid biopsy enters the clinic—implementation issues and future challenges. Nat Rev Clin Oncol. 2021;18:297–312.
Fici P. Cell-free DNA in the liquid biopsy context: role and differences between ctDNA and CTC marker in cancer management. Methods Mol Biol. 2019;4:47–73.
Vitale SR, Helmijr JA, Gerritsen M, Coban H, van Dessel LF, Beije N, et al. Detection of tumor-derived extracellular vesicles in plasma from patients with solid cancer. BMC Cancer. 2021;21:315.
Zhou B, Xu K, Zheng X, Chen T, Wang J, Song Y, et al. Application of exosomes as liquid biopsy in clinical diagnosis. Signal Transduct Target Ther. 2020;5:144.
Jouida A, McCarthy C, Fabre A, Keane MP. Exosomes: a new perspective in EGFR-mutated lung cancer. Cancer Metastasis Rev. 2021;40:589–601.
Krug AK, Enderle D, Karlovich C, Priewasser T, Bentink S, Spiel A, et al. Improved EGFR mutation detection using combined exosomal RNA and circulating tumor DNA in NSCLC patient plasma. Ann Oncol. 2018;29:700–6.
Bronkhorst AJ, Ungerer V, Holdenrieder S. The emerging role of cell-free DNA as a molecular marker for cancer management. Biomol Detect Quantif. 2019;17:100087.
Torchilin VP. Recent advances with liposomes as pharmaceutical carriers. Nat Rev Drug Discov. 2005;4:145–60.
Petersen AL, Hansen AE, Gabizon A, Andresen TL. Liposome imaging agents in personalized medicine. Adv Drug Deliv Rev. 2012;64:1417–35.
Al-Jamal WT, Al-Jamal KT, Tian B, Cakebread A, Halket JM, Kostarelos K. Tumor targeting of functionalized quantum dot−liposome hybrids by intravenous administration. Mol Pharmacol. 2009;6:520–30.
Wang QCY. Multifunctional quantum dots and liposome complexes in drug delivery. J Biomed Res. 2018;32:91–106.
Lamichhane N, Udayakumar T, D’Souza W, Simone Ii C, Raghavan S, Polf J, et al. Liposomes: clinical applications and potential for image-guided drug delivery. Molecules. 2018;23:288.
Martínez-González R, Estelrich J, Busquets M. Liposomes loaded with hydrophobic iron oxide nanoparticles: suitable T2 contrast agents for MRI. Int J Mol Sci. 2016;17:1209.
Portnoy E, Nizri E, Golenser J, Shmuel M, Magdassi S, Eyal S. Imaging the urinary pathways in mice by liposomal indocyanine green. Nanomed Nanotechnol Biol Med. 2015;11:1057–64.
Xing J, Liu D, Zhou G, Li Y, Wang P, Hu K, et al. Liposomally formulated phospholipid-conjugated novel near-infrared fluorescence probe for particle size effect on cellular uptake and biodistribution in vivo. Colloids Surf B Biointerfaces. 2018;161:588–96.
Shen J, Kim H-C, Wolfram J, Mu C, Zhang W, Liu H, et al. A liposome encapsulated ruthenium polypyridine complex as a theranostic platform for triple-negative breast cancer. Nano Lett. 2017;17:2913–20.
Li S, Goins B, Phillips WT, Bao A. Remote-loading labeling of liposomes with99mTc-BMEDA and its stability evaluation: effects of lipid formulation and pH/chemical gradient. J Liposome Res. 2010;21:17–27.
Erdogan S, Medarova ZO, Roby A, Moore A, Torchilin VP. Enhanced tumor MR imaging with gadolinium-loaded polychelating polymer-containing tumor-targeted liposomes. J Magn Reson Imaging. 2008;27:574–80.
Xu B, Ghaghada KB, Sato AF, Starosolski ZA, Berg J, Vail DM. Computed tomography imaging of solid tumors using a liposomal-iodine contrast agent in companion dogs with naturally occurring cancer. PLoS ONE. 2016;11:e0152718.
Zhou T, Cai W, Yang H, Zhang H, Hao M, Yuan L, et al. Annexin V conjugated nanobubbles: A novel ultrasound contrast agent for in vivo assessment of the apoptotic response in cancer therapy. J Control Release. 2018;276:113–24.
Wu B, Wan B, Lu ST, Deng K, Li XQ, Wu BL, et al. Near-infrared light-triggered theranostics for tumor-specific enhanced multimodal imaging and photothermal therapy. Int J Nanomed. 2017;12:4467–78.
Madamsetty VS, Paul MK, Mukherjee A, Mukherjee S. Functionalization of nanomaterials and their application in melanoma cancer theranostics. ACS Biomater Sci Eng. 2019;6:167–81.
Muthu MS, Feng SS. Theranostic liposomes for cancer diagnosis and treatment: current development and pre-clinical success. Expert Opin Drug Deliv. 2012;10:151–5.
Martinez JO, Molinaro R, Hartman KA, Boada C, Sukhovershin R, De Rosa E, et al. Biomimetic nanoparticles with enhanced affinity towards activated endothelium as versatile tools for theranostic drug delivery. Theranostics. 2018;8:1131–45.
Zhang X, Wang B, Xia Y, Zhao S, Tian Z, Ning P, et al. In vivo and in situ activated aggregation-induced emission probes for sensitive tumor imaging using tetraphenylethene-functionalized trimethincyanines-encapsulated liposomes. ACS Appl Mater Interfaces. 2018;10:25146–53.
Chen Q, Liang C, Sun X, Chen J, Yang Z, Zhao H, et al. H2O2-responsive liposomal nanoprobe for photoacoustic inflammation imaging and tumor theranostics via in vivo chromogenic assay. Proc Natl Acad Sci USA. 2017;114:5343–8.
Wolfers J, Lozier A, Raposo G, Regnault A, Théry C, Masurier C, et al. Tumor-derived exosomes are a source of shared tumor rejection antigens for CTL cross-priming. Nat Med. 2001;7:297–303.
Dai S, Wan T, Wang B, Zhou X, Xiu F, Chen T, et al. More efficient induction of HLA-A*0201-Restricted and carcinoembryonic antigen (CEA)–specific CTL response by immunization with exosomes prepared from heat-stressed CEA-positive tumor cells. Clin Cancer Res. 2005;11:7554–63.
Clayton A, Mitchell JP, Court J, Mason MD, Tabi Z. Human tumor-derived exosomes selectively impair lymphocyte responses to interleukin-2. Cancer Res. 2007;67:7458–66.
Xu Z, Zeng S, Gong Z, Yan Y. Exosome-based immunotherapy: a promising approach for cancer treatment. Mol Cancer. 2020;19:160.
Théry C, Boussac M, Véron P, Ricciardi-Castagnoli P, Raposo G, Garin J, et al. Proteomic analysis of dendritic cell-derived exosomes: a secreted subcellular compartment distinct from apoptotic vesicles. J Immunol Res. 2001;166:7309–18.
Théry C, Ostrowski M, Segura E. Membrane vesicles as conveyors of immune responses. Nat Rev Immunol. 2009;9:581–93.
Choi JU, Park IK, Lee YK, Hwang SR. The biological function and therapeutic potential of exosomes in cancer: exosomes as efficient nanocommunicators for cancer therapy. Int J Mol Sci. 2020;21:7363.
Segura E, Nicco C, Lombard BRR, Véron P, Raposo GA, Batteux FDR, et al. ICAM-1 on exosomes from mature dendritic cells is critical for efficient naive T-cell priming. Blood. 2005;106:216–23.
Zimmer J, Simhadri VR, Reiners KS, Hansen HP, Topolar D, Simhadri VL, et al. Dendritic cells release HLA-B-associated transcript-3 positive exosomes to regulate natural killer function. PLoS ONE. 2008;3:e3377.
Munich S, Sobo-Vujanovic A, Buchser WJ, Beer-Stolz D, Vujanovic NL. Dendritic cell exosomes directly kill tumor cells and activate natural killer cells via TNF superfamily ligands. Oncoimmunology. 2014;1:1074–83.
Paul S, Lal G. The molecular mechanism of natural killer cells function and its importance in cancer immunotherapy. Front Immunol. 2017;8:1124.
Escudier B, Dorval T, Chaput, N, André F, Caby M-P, Novault S, et al. Vaccination of metastatic melanoma patients with autologous dendritic cell (DC) derived-exosomes: results of thefirst phase I clinical trial. J Transl Med. 2005;3:10. https://doi.org/10.1186/1479-5876-3-10.
Morse MA, Garst J, Osada T, Khan S, Hobeika A, Clay TM, et al. A phase I study of dexosome immunotherapy in patients with advanced non-small cell lung cancer. J Transl Med. 2005;3:9.
Olejarz W, Dominiak A, Żołnierzak A, Kubiak-Tomaszewska G, Lorenc T. Tumor-derived exosomes in immunosuppression and immunotherapy. J Immunol Res. 2020;2020:1–11.
Zhang X, Yuan X, Shi H, Wu L, Qian H, Xu W. Exosomes in cancer: small particle, big player. J Hematol Oncol. 2015;8:83.
Andre F, Schartz NEC, Movassagh M, Flament C, Pautier P, Morice P, et al. Malignant effusions and immunogenic tumour-derived exosomes. Lancet. 2002;360:295–305.
Zitvogel L, Regnault A, Lozier A, Wolfers J, Flament C, Tenza D, et al. Eradication of established murine tumors using a novel cell-free vaccine: dendritic cell derived exosomes. Nat Med. 1998;4:594–600.
Marton A, Vizler C, Kusz E, Temesfoi V, Szathmary Z, Nagy K, et al. Melanoma cell-derived exosomes alter macrophage and dendritic cell functions in vitro. Immunol Lett. 2012;148:34–8.
Yao Y, Chen L, Wei W, Deng X, Ma L, Hao S. Tumor cell-derived exosome-targeted dendritic cells stimulate stronger CD8+ CTL responses and antitumor immunities. Biochem Biophys Res Commun. 2013;436:60–5.
Joffre OP, Segura E, Savina A, Amigorena S. Cross-presentation by dendritic cells. Nat Rev Immunol. 2012;12:557–69.
Schwendener RA. Liposomes as vaccine delivery systems: a review of the recent advances. Ther Adv Vaccines. 2014;2:159–82.
Yuba E, Kono Y, Harada A, Yokoyama S, Arai M, Kubo K, et al. The application of pH-sensitive polymer-lipids to antigen delivery for cancer immunotherapy. Biomaterials. 2013;34:5711–21.
Hirayama M, Tomita Y, Yuno A, Tsukamoto H, Senju S, Imamura Y, et al. An oncofetal antigen, IMP-3-derived long peptides induce immune responses of both helper T cells and CTLs. Oncoimmunology. 2016;5:e1123368.
Yoshizaki Y, Yuba E, Sakaguchi N, Koiwai K, Harada A, Kono K. pH-sensitive polymer-modified liposome-based immunity-inducing system: effects of inclusion of cationic lipid and CpG-DNA. Biomaterials. 2017;141:272–83.
Yuba E, Yamaguchi A, Yoshizaki Y, Harada A, Kono K. Bioactive polysaccharide-based pH-sensitive polymers for cytoplasmic delivery of antigen and activation of antigen-specific immunity. Biomaterials. 2017;120:32–45.
Park J, Wrzesinski SH, Stern E, Look M, Criscione J, Ragheb R, et al. Combination delivery of TGF-β inhibitor and IL-2 by nanoscale liposomal polymeric gels enhances tumour immunotherapy. Nat Mater. 2012;11:895–905.
Xu Z, Wang Y, Zhang L, Huang L. Nanoparticle-delivered transforming growth factor-β siRNA enhances vaccination against advanced melanoma by modifying tumor microenvironment. ACS Nano. 2014;8:3636–45.
Schultheis B, Strumberg D, Santel A, Vank C, Gebhardt F, Keil O, et al. First-in-human phase I study of the liposomal RNA interference therapeutic Atu027 in patients with advanced solid tumors. J Clin Oncol. 2014;32:4141–8.
Wagner MJ, Mitra R, McArthur MJ, Baze W, Barnhart K, Wu SY, et al. Preclinical mammalian safety studies of EPHARNA (DOPC Nanoliposomal EphA2-Targeted siRNA). Mol Cancer Ther. 2017;16:1114–23.
Yi K, Rong Y, Huang L, Tang X, Zhang Q, Wang W, et al. Aptamer–exosomes for tumor theranostics. ACS Sensors. 2021;6:1418–29.
He C, Zheng S, Luo Y, Wang B. Exosome theranostics: biology and translational medicine. Theranostics. 2018;8:237–55.
Cordonnier M, Chanteloup G, Isambert N, Seigneuric R, Fumoleau P, Garrido C, et al. Exosomes in cancer theranostic: diamonds in the rough. Cell Adh Migr. 2017;11:151–63.
Yang D, Zhang W, Zhang H, Zhang F, Chen L, Ma L, et al. Progress, opportunity, and perspective on exosome isolation - efforts for efficient exosome-based theranostics. Theranostics. 2020;10:3684–707.
Chen D-W, Cheng L, Huang F, Cheng L, Zhu Y, Hu Q, et al. GE11-modified liposomes for non-small cell lung cancer targeting: preparation, ex vitro and in vivo evaluation. Int J Nanomed. 2014;9:921–35.
Lin C, Zhang X, Chen H, Bian Z, Zhang G, Riaz MK, et al. Dual-ligand modified liposomes provide effective local targeted delivery of lung-cancer drug by antibody and tumor lineage-homing cell-penetrating peptide. Drug Deliv. 2018;25:256–66.
Erten A, Wrasidlo W, Scadeng M, Esener S, Hoffman RM, Bouvet M, et al. Magnetic resonance and fluorescence imaging of doxorubicin-loaded nanoparticles using a novel in vivo model. Nanomed Nanotechnol Biol Med. 2010;6:797–807.
Cittadino E, Ferraretto M, Torres E, Maiocchi A, Crielaard BJ, Lammers T, et al. MRI evaluation of the antitumor activity of paramagnetic liposomes loaded with prednisolone phosphate. Eur J Pharm Sci. 2012;45:436–41.
Saraf S, Jain A, Tiwari A, Verma A, Panda PK, Jain SK. Advances in liposomal drug delivery to cancer: an overview. J Drug Deliv Sci Technol. 2020;56:101549.
Seleci M, Ag Seleci D, Scheper T, Stahl F. Theranostic liposome–nanoparticle hybrids for drug delivery and bioimaging. Int J Mol Sci. 2017;18:1415.
Madamsetty VS, Mukherjee A, Mukherjee S. Recent trends of the bio-inspired nanoparticles in cancer theranostics. Front Pharmacol. 2019;10:1264.
Li YJ, Wu JY, Liu J, Xu W, Qiu X, Huang S, et al. Artificial exosomes for translational nanomedicine. J Nanobiotechnol. 2021;19:242.
Sato YT, Umezaki K, Sawada S, Mukai S-a, Sasaki Y, Harada N, et al. Engineering hybrid exosomes by membrane fusion with liposomes. Sci Rep. 2016;6:21933.
Lin Y, Wu J, Gu W, Huang Y, Tong Z, Huang L, et al. Exosome-liposome hybrid nanoparticles deliver CRISPR/Cas9 system in MSCs. Adv Sci. 2018;5:1700611.
Yang Y, Hong Y, Nam G-H, Chung JH, Koh E, Kim I-S. Virus-mimetic fusogenic exosomes for direct delivery of integral membrane proteins to target cell membranes. Adv Mater. 2017;29:1605604.
Gao X, Li S, Ding F, Fan H, Shi L, Zhu L, et al. Rapid detection of exosomal microRNAs using virus‐mimicking fusogenic vesicles. Angew Chem Int Ed. 2019;58:8719–23.
Rayamajhi S, Nguyen TDT, Marasini R, Aryal S. Macrophage-derived exosome-mimetic hybrid vesicles for tumor targeted drug delivery. Acta Biomater. 2019;94:482–94.
Cheng L, Zhang X, Tang J, Lv Q, Liu J. Gene-engineered exosomes-thermosensitive liposomes hybrid nanovesicles by the blockade of CD47 signal for combined photothermal therapy and cancer immunotherapy. Biomaterials. 2021;275:120964.
Xu M, Yang Q, Sun X, Wang Y. Recent advancements in the loading and modification of therapeutic exosomes. Front Bioeng Biotechnol. 2020;8:586130.
Rampado R, Crotti S, Caliceti P, Pucciarelli S, Agostini M. Recent advances in understanding the protein corona of nanoparticles and in the formulation of “Stealthy” nanomaterials. Front Bioeng Biotechnol. 2020;8:166.
Caracciolo G. Liposome–protein corona in a physiological environment: challenges and opportunities for targeted delivery of nanomedicines. Nanomed Nanotechnol Biol Med. 2015;11:543–57.
Tasciotti E, Molinaro R, Taraballi F, Toledano Furman N, Sherman M, Parodi A, et al. Effects of the protein corona on liposome-liposome and liposome-cell interactions. Int J Nanomed. 2016;11:3049–63.
Tóth EÁ, Turiák L, Visnovitz T, Cserép C, Mázló A, Sódar BW, et al. Formation of a protein corona on the surface of extracellular vesicles in blood plasma. J Extracell Vesicles. 2021;10:e12140.
Varga Z, Fehér B, Kitka D, Wacha A, Bóta A, Berényi S, et al. Size measurement of extracellular vesicles and synthetic liposomes: the impact of the hydration shell and the protein corona. Colloids Surf B Biointerfaces. 2020;192:111053.
Skliar M, Chernyshev VS, Belnap DM, Sergey GV, Al-Hakami SM, Bernard PS, et al. Membrane proteins significantly restrict exosome mobility. Biochem Biophys Res Commun. 2018;501:1055–9.
Busatto S, Yang Y, Walker SA, Davidovich I, Lin WH, Lewis-Tuffin L, et al. Brain metastases-derived extracellular vesicles induce binding and aggregation of low-density lipoprotein. J Nanobiotechnol. 2020;18:162.
Palchetti S, Caputo D, Digiacomo L, Capriotti A, Coppola R, Pozzi D, et al. Protein corona fingerprints of liposomes: new opportunities for targeted drug delivery and early detection in pancreatic cancer. Pharmaceutics. 2019;11:31.
Park W, Heo YJ, Han DK. New opportunities for nanoparticles in cancer immunotherapy. Biomater Res. 2018;22:24.
Velpurisiva P, Gad A, Piel B, Jadia R, Rai P. Nanoparticle design strategies for effective cancer immunotherapy. J Biomed Sci. 2017;2:64–77.
Parak K. Rational drug loading of liposomes revisited. J Control Release. 2017;252:125.
Ait-Oudhia S, Mager D, Straubinger R. Application of pharmacokinetic and pharmacodynamic analysis to the development of liposomal formulations for oncology. Pharmaceutics. 2014;6:137–74.
Madamsetty VS, Mukherjee A, Paul MK. Bioinspired nanoparticles-based drug delivery systems for cancer theranostics. In: Patra CAI, Ayaz M, Khalil AT, Mukherjee S, Ovais M, editors. Biogenic nanoparticles for cancer theranostics, chap 9. Elsevier; 2021. p. 189–228.
Beltrán-Gracia E, López-Camacho A, Higuera-Ciapara I, Velázquez-Fernández JB, Vallejo-Cardona AA. Nanomedicine review: clinical developments in liposomal applications. Cancer Nanotechnol. 2019;10:11.
Kim DH, Kothandan VK, Kim HW, Kim KS, Kim JY, Cho HJ, et al. Noninvasive assessment of exosome pharmacokinetics in vivo: a review. Pharmaceutics. 2019;11:649.
Wolf T, Baier SR, Zempleni J. The intestinal transport of bovine milk exosomes is mediated by endocytosis in human colon carcinoma Caco-2 cells and rat small intestinal IEC-6 cells. J Nutr. 2015;145:2201–6.
Tian T, Zhu YL, Zhou YY, Liang GF, Wang YY, Hu FH, et al. Exosome uptake through clathrin-mediated endocytosis and macropinocytosis and mediating miR-21 delivery. J Biol Chem. 2014;289:22258–67.
Kim MS, Haney MJ, Zhao Y, Yuan D, Deygen I, Klyachko NL, et al. Engineering macrophage-derived exosomes for targeted paclitaxel delivery to pulmonary metastases: in vitro and in vivo evaluations. Nanomed Nanotechnol Biol Med. 2018;14:195–204.
Yuan D, Zhao Y, Banks WA, Bullock KM, Haney M, Batrakova E, et al. Macrophage exosomes as natural nanocarriers for protein delivery to inflamed brain. Biomaterials. 2017;142:1–12.
Morishita M, Takahashi Y, Nishikawa M, Ariizumi R, Takakura Y. Enhanced class I tumor antigen presentation via cytosolic delivery of exosomal cargos by tumor-cell-derived exosomes displaying a pH-sensitive fusogenic peptide. Mol Pharmacol. 2017;14:4079–86.
He H, Yuan D, Wu Y, Cao Y. Pharmacokinetics and pharmacodynamics modeling and simulation systems to support the development and regulation of liposomal drugs. Pharmaceutics. 2019;11:110.
Rowland M. Physiologically-based pharmacokinetic (PBPK) modeling and simulations principles, methods, and applications in the pharmaceutical industry. CPT Pharmacomet Syst Pharmacol. 2013;2:e55.
Yellepeddi V, Rower J, Liu X, Kumar S, Rashid J, Sherwin CMT. State-of-the-art review on physiologically based pharmacokinetic modeling in pediatric drug development. Clin Pharmacokinet. 2018;58:1–13.
Acknowledgements
BB acknowledges Dr. Jay M. Lee for providing research support. MKP acknowledges S. Dubinett and B. Gomperts from UCLA for providing constant support and mentoring.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing interests.
Rights and permissions
About this article
Cite this article
Mukherjee, A., Bisht, B., Dutta, S. et al. Current advances in the use of exosomes, liposomes, and bioengineered hybrid nanovesicles in cancer detection and therapy. Acta Pharmacol Sin 43, 2759–2776 (2022). https://doi.org/10.1038/s41401-022-00902-w
Received:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/s41401-022-00902-w
Keywords
This article is cited by
-
Exosomes in cancer nanomedicine: biotechnological advancements and innovations
Molecular Cancer (2025)
-
A state-of-the-art review of the recent advances of theranostic liposome hybrid nanoparticles in cancer treatment and diagnosis
Cancer Cell International (2025)
-
Innovative approach to the detection of circulating tumor biomarkers: multi-dimensional application of liposome technology
Lipids in Health and Disease (2025)
-
Microglia-targeting nanosystems that cooperatively deliver Chinese herbal ingredients alleviate behavioral and cognitive deficits in Alzheimer’s disease model mice
Journal of Nanobiotechnology (2025)
-
Updates and current states on liposomal vehicles for tumor targeting: precision therapy in the spotlight
Cancer Nanotechnology (2025)
