Nanoparticle-Drug Conjugate Applications in Cancer Therapy

Nanoparticle-drug conjugates represent a convergence of nanotechnology and pharmacology, designed to improve the selectivity, pharmacokinetics and therapeutic index of anticancer agents. By covalently or non-covalently attaching small-molecule drugs to nanoscale carriers, it becomes possible to exploit passive accumulation via the enhanced permeability and retention effect and to introduce active targeting motifs that recognise tumour-associated markers. Such conjugates can modulate drug release kinetics, reduce systemic toxicity and remodel the tumour microenvironment to enhance immune recognition. Across a range of solid tumours—including colorectal, glioblastoma and metastatic solid cancers—these platforms have been engineered from diverse materials such as cyclodextrin polymers, lipids, peptides and inorganic backbones.

Current efforts address key challenges: achieving controlled release within the tumour milieu, overcoming biological barriers such as the blood–brain barrier, and integrating immunomodulatory functions. Advances include the incorporation of cleavable linkers responsive to pH or redox conditions, surface modification with tumour-homing ligands, and the combination of cytotoxics with immunotherapeutic agents. Together, these strategies aim to translate preclinical promise into robust clinical outcomes, offering new avenues for precision oncology.

Research from Nature Portfolio

Recent studies have developed non-covalent channel-type nanoparticles formed by the self-assembly of mannose-modified γ-cyclodextrin with the multikinase inhibitor regorafenib. These host–guest complexes not only serve as carriers but also contribute to tumour microenvironment reprogramming. The mannose decoration promotes uptake by tumour-associated macrophages, attenuating their pro-tumour activation, while the channel-type architecture optimises drug pharmacokinetics and biodistribution. In preclinical models of colitis-associated colorectal cancer and syngeneic mouse grafts, this formulation demonstrated targeted suppression of tumour cell proliferation, inhibition of neovascularisation and remodelling of inflammatory stroma, leading to improved safety and antitumour efficacy.

Nanoparticle-Drug Conjugate Applications in Cancer Therapy publication trend

The graph below shows the total number of articles in nanoparticle-drug conjugate applications in cancer therapy across all publications each year (not limited to Nature Index journals).

Technical terms

Nanoparticle-drug conjugate: A hybrid construct in which therapeutic molecules are chemically or physically bound to nanoscale carriers to improve delivery and release kinetics.

Enhanced permeability and retention (EPR) effect: Passive accumulation of nanoparticles in tumours due to leaky vasculature and impaired lymphatic drainage.

Tumour microenvironment (TME): The complex milieu surrounding tumour cells, including immune cells, stroma and extracellular matrix components.

Cyclodextrin: A cyclic oligosaccharide used as a host molecule for non-covalent drug complexation and carrier fabrication.

Pharmacokinetics: The study of drug absorption, distribution, metabolism and excretion over time.

Host–guest complexation: Supramolecular interaction between a host molecule (e.g., cyclodextrin) and a guest drug, enabling reversible binding.

References

1. Cyclodextrin-based host-guest complexes loaded with regorafenib for colorectal cancer treatment. Nature Communications (2021).
2. Preclinical effects of CRLX101, an investigational camptothecin-containing nanoparticle drug conjugate, on treating glioblastoma multiforme via apoptosis and antiangiogenesis. Oncotarget (2016).
3. Anticancer Nanotherapeutics in Clinical Trials: The Work behind Clinical Translation of Nanomedicine. International Journal of Molecular Sciences (2022).
4. A Systematic Review of Clinical Trials on the Efficacy and Safety of CRLX101 Cyclodextrin-Based Nanomedicine for Cancer Treatment. Pharmaceutics (2023).