Smart Nanocarriers for Targeted Cancer Therapy: A Comprehensive Review

ABSTRACT Cancer is one of the leading causes of morbidity and mortality worldwide. Although conventional cancer therapies such as surgery, chemotherapy and radiotherapy can improve cancer survival, their efficacy is often limited by poor tumour selectivity and damage to healthy tissues. Conventional anticancer drugs may also have poor aqueous solubility, low bioavailability, rapid clearance, nonspecific distribution and multidrug resistance. These limitations have led to the development of advanced drug-delivery systems, particularly smart nanocarriers. Smart nanocarriers are engineered nanoscale systems that enhances the pharmacokinetics, improve biodistribution promotes the preferential tumour accumulation, and enable controlled drug liberation. They can be engineered to respond to specific internal or external stimuli associated with tumour tissues. Endogenous stimuli include acidic tumour pH, overexpressed enzymes and intracellular redox conditions, whereas exogenous stimuli include temperature, light and magnetic fields. Targeting can be done through passive targeting mainly based on the enhanced permeability and retention (EPR) effect, active targeting using ligands such as antibodies, peptides, aptamers and folic acid, stimuli-responsive targeting and biomimetic approaches using cell membranes. Several nanocarrier systems including liposomes, polymeric nanoparticles, micelles, dendrimers, gold nanoparticles, quantum dots, solid lipid nanoparticles and hybrid nanocarriers have been investigated for cancer therapy. Multifunctional systems can simultaneously deliver chemotherapeutic agents, proteins, nucleic acids, and imaging agents, thereby combining therapy and diagnosis. Despite their advantages, clinical translation remains a challenge due to tumour heterogeneity, biological barriers, nanoparticle stability, toxicity, manufacturing complexity, and the variability of the EPR effect. Continued research in nanotechnology, tumour biology and personalized medicine may help improve the clinical application of smart nanocarriers in cancer treatment.