Nanoparticle-Mediated Chemotherapy Optimization

Abstract

Nanoparticle-mediated drug delivery represents the most clinically advanced application of nanotechnology to oncological chemotherapy, offering the ability to encapsulate cytotoxic agents within engineered carriers that modify their biodistribution, prolong systemic circulation, and exploit tumour-specific delivery mechanisms to improve the therapeutic index of drugs whose free-form toxicity profiles severely limit achievable tumour doses. The clinical landscape of approved nanoparticle chemotherapy formulations -- Abraxane (nab-paclitaxel), Doxil (PEGylated liposomal doxorubicin), Onivyde (liposomal irinotecan), and Vyxeos (dual-drug daunorubicin/cytarabine liposome) -- provides a validated pharmacological foundation demonstrating that nanoparticle delivery can alter the clinical activity and adverse effect profiles of established chemotherapy agents in meaningful ways. This comprehensive review evaluates 247 nanoparticle chemotherapy formulations -- spanning polymeric nanoparticles, liposomes, albumin-bound formulations, dendrimers, metallic nanoparticles, and hybrid platforms -- from 84 clinical and preclinical studies published 2015-2022, assessing tumour accumulation efficiency, drug release kinetics, combination chemotherapy co-encapsulation fidelity, and clinical response rates versus free-drug comparators. Albumin-bound nanoparticles (nab-technology) achieved the highest clinical response rate improvement over free drug (ORR +18.4 percentage points; p < 0.001) across breast; pancreatic; and lung cancer indications. Stimuli-responsive nanoparticles -- releasing drug specifically in response to tumour microenvironment pH (6.5-6.8), hypoxia, or matrix metalloprotease activity -- achieved 2.4-fold higher intratumoural drug concentrations than passive EPR-only formulations in preclinical models, though clinical translation remains challenging. A Nanoparticle Chemotherapy Optimisation Index (NCOI) integrating drug loading, release kinetics, tumour accumulation, and tolerability is developed and validated across the 247 formulations, providing a standardised framework for rational nanoparticle chemotherapy design.