Nanoparticle Drug Delivery Systems for Overcoming Multidrug Resistance in Cancer Therapy

Multidrug resistance (MDR) remains a formidable obstacle in effective cancer chemotherapy, driven largely by the overexpression of efflux pumps and alterations in cellular apoptosis pathways. Nanoparticle drug delivery systems offer a multifaceted approach to circumvent these mechanisms by improving drug solubility, enhancing tumour targeting and modulating intracellular trafficking. Key strategies include surface modification with ligands or polymers to achieve receptor-mediated uptake, incorporation of efflux-pump inhibitors to block drug export, and design of stimuli-responsive carriers that release payloads in response to pH, enzymes or redox gradients within the tumour microenvironment. Such nanoformulations not only increase intratumoural drug concentration but also permit co-delivery of chemotherapeutics with siRNA, chemosensitisers or photosensitisers to synergise antitumour effects. The global significance of these platforms is underscored by their potential to revitalise established drugs, reduce systemic toxicity and address resistant malignancies across a spectrum of solid and haematological cancers.

Research from Nature Portfolio

Recent studies have demonstrated that D-α-tocopheryl polyethylene glycol succinate (TPGS)-modified proniosomes markedly enhance the oral bioavailability and antitumour efficacy of docetaxel. These proniosomal formulations form stable niosomes upon hydration, exhibiting sustained drug release in simulated gastrointestinal fluids and improved intestinal permeability in Caco-2 and ex vivo gut models. In murine xenograft experiments, oral administration of the docetaxel proniosomes achieved significantly higher plasma exposure and tumour growth inhibition compared with conventional docetaxel solutions, illustrating a scalable approach to overcome P-glycoprotein-mediated drug efflux and reduce dosing frequency.

Nanoparticle Drug Delivery Systems for Overcoming Multidrug Resistance in Cancer Therapy publication trend

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

Technical terms

Multidrug resistance (MDR): The ability of cancer cells to evade the effects of multiple structurally unrelated chemotherapeutic agents, often via overexpression of efflux transporters.

TPGS (D-α-tocopheryl polyethylene glycol succinate): A water-soluble vitamin E derivative used as a surfactant, solubiliser and P-glycoprotein inhibitor in nanoparticle formulations.

Proniosomes: Dry, free-flowing carrier powders that convert into niosomes upon hydration, enabling sustained and targeted drug release.

Reactive oxygen species (ROS): Oxygen-derived free radicals and peroxides that, at elevated levels, can induce apoptosis in cancer cells.

References

1. Improved Bioavailability and Antitumor Effect of Docetaxel by TPGS Modified Proniosomes: In Vitro and In Vivo Evaluations. Scientific Reports (2017).
2. Sertaconazole-repurposed nanoplatform enhances lung cancer therapy via CD44-targeted drug delivery. Journal of Experimental & Clinical Cancer Research (2023).
3. Resveratrol loaded polymeric micelles for theranostic targeting of breast cancer cells. Nanotheranostics (2021).
4. Folic acid modified TPGS as a novel nano-micelle for delivery of nitidine chloride to improve apoptosis induction in Huh7 human hepatocellular carcinoma. BMC Pharmacology and Toxicology (2021).