Multifunctional pH-responsive nanogel for malaria and cancer treatment: Hitting two targets with one arrow

Malaria and cancer have been considered deadly diseases around the world. Cancer and malaria both have high incidence rates despite numerous research efforts to develop effective strategies for mitigating the burden of these two distinct ailments. Herein, pH-responsive nanogel based on methacrylic acid-functionalized with bovine serum albumin (PMAA-BSA) with an average diameter of ∼75 nm was fabricated for smart delivery of chloroquine (CQ). These nanoplatforms exhibited high drug loading efficacy (26.42%). Also it displayed a higher CQ release rate (92.03%) under simulated acidic microenvironment of the digestive vacuole (DV) and tumor tissue whereas 40.01% CQ was released under a neutral physiological environment. More importantly, this unique pH-responsive nanogel lowered the IC50 of CQ by approximately 2.8-fold and 1.9-fold in MCF-7 cells at 24 and 48 h, respectively. Interestingly, blank PMAA-BSA nanogels displayed anti-plasmodial activity and no one to the best of our knowledge has developed a drug vehicle with inherent antimalarial features. PMAA-BSA-CQ through its synergistic effects exhibited great anti-plasmodial activity under both in vitro and in vivo conditions. Furthermore, PMAA-BSA-CQ fully eradicate the parasites in Plasmodium berghei infected mice and prolonged their survival rate. In conclusion, such pH-responsive nanogel with targeting ability and non-toxicity could be used as a very promising nanoplatform for intracellular and tumor trigger release of antimalarial/anti-cancer drugs.

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