Smart nano-carriers have attained great significance in the biomedical field due to their versatile and interesting designs with different functionalities. The initial stages of the development of nanocarriers mainly focused on the guest loading efficiency, biocompatibility of the host and the circulation time. Later the requirements of less side effects with more efficacy arose by attributing targetability and stimuli-responsive characteristics to nano-carriers along with their bio- compatibility. Researchers are utilizing many stimuli-responsive polymers for the better release of the guest molecules at the targeted sites. Among these, pH-triggered release achieves increasing importance because of the pH variation in different organ and cancer cells of acidic pH. This specific feature is utilized to release the guest molecules more precisely in the targeted site by designing polymers having specific functionality with the pH dependent morphology change characteristics. In this review, we mainly concert on the pH-responsive polypeptides and some interesting nano-carrier designs for the effective theranostic applications. Also, emphasis is made on pharmaceutical application of the different nano-carriers with respect to the organ, tissue and cellular level pH environment.

A series of ABC triblock poly(N-isopropylacrylamide)75-block-poly(L-lysine)35-block-poly(L-histidine)n (p(NIPAM)75-b-p(Lys)35-b-p(His)N) (N = 35,50,75,100) copolymer bio-conjugates were prepared by combining reversible addition-fragmentation chain transfer polymerization and fast ring-opening polymerization of N-carboxyanhydride a-amino acid using 1,3-dicyclohexylimidazolium hydrogen carbonate as a catalyst. All the resulting triblock copolymers self-assembled into spherical micellar aggregates in aqueous solution, irrespective of the chain length of the histidine block. The micellar aggregates encapsulated the anticancer drug doxorubicin (Dox) and exhibited high drug loading efficiency. Temperature and pH stimuli were applied to investigate the controlled release of Dox. The non-cytotoxic nature of the polymers was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cellular uptake of the Dox-loaded micelles revealed that the micelles successfully release Dox in cancer cells in response to pH- and temperature-induced morphological change. In-vitro studies further confirmed that the Dox-loaded triblock copolymer micelle is an excellent platform for drug delivery.