Improving Nanoparticle Delivery in Cancer Nanomedicine: Insights Based on Biodistribution Research

Abstract

Introduction: Cancer is one of the leading causes of death worldwide, and while chemotherapy and radiotherapy remain primary treatments, they are limited by poor tumour specificity, systemic toxicity and drug resistance. Nanoparticle (NP)-based drug delivery offers a promising alternative, with improved solubility, controlled release, and targeted delivery, to enhance efficacy and minimise adverse effects. However, delivery remains inefficient, often resulting in off-target accumulation, immune clearance, renal filtration, and poor tumour penetration. This review explores how biological and physiological barriers limit NP-based delivery and evaluates strategies such as biomimetic cloaking, synthetic surface modifications, and tumour-responsive targeting to improve therapeutic accumulation and efficacy.

Methods: This review looked at strategies to improve NP delivery in cancer by analysing their biodistribution and interaction with biological surfaces and barrier. Peer-reviewed studies were identified through PubMed and Google Scholar using keywords such as “nanoparticle clearance”, “tumour penetration”, “immune evasion”, “biomimetic cloaking”, and “PEGylation”. Articles published between 1990 and 2025 were included if they investigated NP delivery barriers, biodistribution, or design strategies that are specific to cancer. Review articles that provided contextual backgrounds were also considered.

Results: Biomimetic cloaking of nanoparticles improves NP circulation and tumour accumulation. Red blood cell membrane-coated NPs evade immune recognition and reduce opsonisation by displaying self-marker proteins that prolong circulation. Platelet membrane cloaking can improve tumour targeting by taking advantage of platelet interactions with damaged vasculature and circulating tumour cells. PEGylation forms a hydrophilic barrier, preventing opsonisation and clearance by macrophages. Zwitterionic coatings neutralise surface charge to reduce renal filtration, while NP size optimisation (50-150 nm) helps balance circulation time and tumour permeability. However, tumour penetration remains a challenge, particularly in solid tumours with high interstitial pressure.

Implications: These findings show the importance of integrated NP systems that combine immune evasion, tumour targeting, and local release mechanisms. These innovations align with the shift towards personalised and biomimetic therapies, improving targeted cancer treatments. Continued research is needed to bridge the gap between preclinical findings and clinical applications, improving cancer treatment outcomes. Future work should focus on scalable, low-immunogenic solutions to the systemic and tumour-specific barriers to unlock the full potential of cancer nanomedicine.