Tumor Biology; Usefulness of Thermosensitive and pH Sensitive Polymeric Nanoparticles for Tumor Targeting: A Review

Polymeric nanoparticles (PNPs) have attracted the interest of many scientists and have been utilized in an increasing number of fields during the last two decades. The conventional chemotherapeutic agents have poor pharmacokinetic parameters such as non-specific distribution of drugs, the lack of drug specific affinity towards a pathological site, and thus necessitating large dose of a drug to achieve high local concentration in the body leading to systemic toxicity associated with serious side effects. A thorough and precise understanding of tumor microenvironment such as angiogenesis, tumor pH, enhanced permeation and retention (EPR) effect, abnormal lymphatics, multidrug resistance (MDR) and high interstitial fluid pressure, allows designing drug delivery systems that specifically target anti-cancer drugs to tumors. An attempt has been made in this article to highlight the temperature and pH sensitive PNPs, and PNPs with dual and double response to both temperature and pH that have a distinct capacity to target tumors with limited effect on healthy tissues. The stimuli responsive nanoparticles are classified based on their mechanism of response to temperature and pH. Structure of the polymer, methods of drug loading, and characterization of PNPs are elucidated. Keywords: Polymeric nanoparticles; pH sensitive polymers; Thermosensitive polymers; Tumor microenvironment; Multidrug resistance; Drug loading.