pH-Responsive Polypeptide-Based Smart Nano-Carriers for Theranostic Applications

Abstract

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.

Nanomedicine Fight against Antibacterial Resistance: An Overview of the Recent Pharmaceutical Innovations

“…pH-triggered antibiotic release achieves increasing importance nowadays. Designing polymers with pH-responsive materials, for example poly-l-histidine [190], comes with the possibility of pH triggered surface charge switching in acidic medium of the infected bacteria. This specific feature is utilized to maximize the attraction force to the bacterial cell wall having negative charge and hence release the antibacterial drug more precisely in the targeted site.…”

Multi-Smart and Scalable Bioligands-Free Nanomedical Platform for Intratumorally Targeted Tambjamine Delivery, a Difficult to Administrate Highly Cytotoxic Drug

“…Several researches have reported that differences in pH between tumor and healthy tissue can be exploited to promote targeted anticancer therapy [ 12 ]. This has led to the exploration of different nanosized systems with pH-responsive properties for cancer treatment [ 13 ]. One example is the development of nanoparticles with a large structure to avoid blood clearance that shrink once pH decreases in tumor, enhancing cell penetration [ 14 ].…”

Advances in Multiple Stimuli-Responsive Drug-Delivery Systems for Cancer Therapy

“…Due to vacuolar proton ATPase-mediated proton influx, the pH value of endosome and lysosome is lower than 6.0, NPs with ionizable groups (including amine, acyl sulfonamide, and imidazole) produce proton sponge effect to increase osmotic pressure in the inner compartment, eventually, realizing endosomal escape with the disruption of the plasma membrane. 69 , 70 Meanwhile, the low pH value of endo/lysosomal is the most widely used to achieve subcellular-targeted drug release by adding acid-sensitive bonds (such as hydrazone bonds) or protonated groups. However, acidic lysosome is common in normal cells not specific to tumor cells, so NPs triggered by lysosomes are needed to combine with other tumor cellular-specific stimuli to prevent off-target effects ( Figure 7 ).…”

“… 71 Additionally, upregulated enzymes also serve as key stimuli for triggering signal turn-on with the significantly reduction of off-target effect owing to the high specificity of enzyme catalysis. 69 The cellular triggered reactions are designed in advance in the physical model, in which the macrostructures of the NPs changed by the over-expressed enzymes can result in a rapid release of payloads through transformation or degradation when the NPs reach the cytoplasm. 72 Among them, hydrolase and redox enzymes are more sensitive which are generally introduced to construct enzyme-triggered responsive NPs.…”