Phytochemical-Based Nanomedicine for Targeting Tumor Microenvironment and Inhibiting Cancer Chemoresistance: Recent Advances and Pharmacological Insights

Cancerremains the leading cause of death and rapidly evolvingdisease worldwide. The understanding of disease pathophysiology hasimproved through advanced research investigation, and several therapeuticstrategies are being used for better cancer treatment. However, theincrease in cancer relapse and metastatic-related deaths indicatethat available therapies and clinically approved chemotherapy drugsare not sufficient to combat cancer. Further, the constant crosstalkbetween tumor cells and the tumor microenvironment (TME) is crucialfor the development, progression, metastasis, and therapeutic responseto tumors. In this regard, phytochemicals with multimodal targetingabilities can be used as an alternative to current cancer therapyby inhibiting cancer survival pathways or modulating TME. However,due to their poor pharmacokinetics and low bioavailability, the successof phytochemicals in clinical trials is limited. Therefore, developingphytochemical-based nanomedicine or phytonanomedicine can improvethe pharmacokinetic profile of these phytochemicals. Herein, the molecularcharacteristics and pharmacological insights of the proposed phytonanomedicinein cancer therapy targeting tumor tissue and altering the characteristicsof cancer stem cells, chemoresistance, TME, and cancer immunity arewell discussed. Further, we have highlighted the clinical perspectiveand challenges of phytonanomedicine in filling the gap in potentialcancer therapeutics using various nanoplatforms. Overall, we havediscussed how clinical success and pharmacological insights couldmake it more beneficial to boost the concept of nanomedicine in theacademic and pharmaceutical fields to counter cancer metastases anddrug resistance.