Nanoparticle-Mediated Drug Delivery Systems in Cancer Therapy

Nanoparticle-mediated drug delivery harnesses materials engineered at the nanoscale to enhance the precision, efficacy and safety of anticancer agents. By encapsulating chemotherapeutics, biological molecules or nucleic acids within biocompatible carriers—such as liposomes, polymeric particles, inorganic frameworks and hybrid constructs—these systems improve drug solubility, circulation time and tumour accumulation. Two principal targeting strategies guide nanoparticle design: passive targeting exploits the enhanced permeability and retention effect of leaky tumour vasculature, while active targeting employs surface ligands to bind tumour-specific receptors. Stimuli-responsive platforms can release cargo in response to endogenous cues (pH, redox potential, enzymes) or exogenous triggers (light, temperature, magnetic fields). Recent advances integrate combination therapies—photodynamic, photothermal or chemodynamic approaches—with immunomodulation to elicit immunogenic cell death and systemic antitumour immunity. Despite encouraging preclinical results, clinical translation remains constrained by manufacturing scale-up, reproducible characterisation, off-target toxicity and regulatory challenges. Global efforts focus on standardising protocols, refining targeting specificity and demonstrating safety in large-scale trials. As the field merges materials science, molecular biology and engineering, nanoparticle-mediated delivery stands poised to deliver personalised cancer therapies with improved therapeutic indices and reduced adverse effects.

Research from Nature Portfolio

Recent studies have critically examined the gap between preclinical promise and clinical performance of targeted nanocarriers. One comprehensive review assessed the principles of passive and active delivery, identifying design considerations—such as ligand density, particle size and surface chemistry—that influence tumour penetration and biodistribution. Recommendations were proposed to prioritise robustness and manufacturability in next-generation actively targeted nanoparticles.

Another investigation introduced an open-source, self-supplying nanoreactor that co-delivers oxygen and hydrogen peroxide to overcome hypoxia limitations in reactive oxygen species-based therapies. This construct comprises mesoporous silica supports loaded with calcium peroxide and a photosensitiser, encapsulated within a phase-change material. Under near-infrared irradiation, controlled heat induces release of oxygen and peroxide, thereby amplifying photodynamic and chemodynamic reactions in the tumour microenvironment.

A further study demonstrated an endoplasmic reticulum-targeting nanosystem combining hollow gold nanospheres, targeting peptides and oxygen-carrying liposomes. Under light irradiation, this platform generated reactive oxygen species within the ER, inducing stress-mediated immunogenic cell death and enhanced dendritic cell activation. The dual photodynamic-photothermal design elicited systemic CD8+ T-cell responses and improved antitumour efficacy in vivo.

Nanoparticle-Mediated Drug Delivery Systems in Cancer Therapy publication trend

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

Technical terms

Nanoparticle: A particulate system with at least one dimension between 1 and 100 nm, used as a carrier for therapeutic and diagnostic agents.

Passive targeting: Accumulation of nanoparticles in tumour tissue via the enhanced permeability and retention (EPR) effect, due to leaky vasculature and poor lymphatic drainage.

Active targeting: Functionalisation of nanoparticle surfaces with ligands (antibodies, peptides) that bind selectively to receptors overexpressed on cancer cells.

Enhanced permeability and retention (EPR) effect: A phenomenon by which nanoparticles preferentially accumulate in tumour tissue because of abnormal tumour blood vessels and impaired lymphatic clearance.

Photodynamic therapy (PDT): A treatment that uses a photosensitising agent activated by light to generate reactive oxygen species that kill cancer cells.

Photothermal therapy (PTT): A modality in which photothermal agents convert light energy into heat to ablate tumour tissue.

Immunogenic cell death (ICD): A form of cell death that releases danger signals and tumour antigens, stimulating an adaptive immune response against cancer.

Stimuli-responsive release: Controlled drug release triggered by specific internal (pH, redox) or external (light, temperature) stimuli.

References

1. Smart nanoparticles for cancer therapy. Signal Transduction and Targeted Therapy (2023).
2. Progressing nanotechnology to improve targeted cancer treatment: overcoming hurdles in its clinical implementation. Molecular Cancer (2023).
3. Nano based drug delivery systems: recent developments and future prospects. Journal of Nanobiotechnology (2018).
4. Progress and challenges towards targeted delivery of cancer therapeutics. Nature Communications (2018).
5. Targeting photodynamic and photothermal therapy to the endoplasmic reticulum enhances immunogenic cancer cell death. Nature Communications (2019).
6. An open source and reduce expenditure ROS generation strategy for chemodynamic/photodynamic synergistic therapy. Nature Communications (2020).