A dual responsive robust human serum albumin‐based nanocarrier for doxorubicin

Abstract

Targeted drug therapy against cancer has been introduced as a smart strategy to combat the unwanted side effects due to systemic administration of chemotherapeutics. A human serum albumin (HSA)‐based nanocarrier was fabricated with the aim to target reductive media and acidic pH of the tumor tissues. α‐Lipoic acid (LA) was applied to increase the number of disulfide bonds in the nanocarrier to target higher glutathione concentrations present in tumor tissues and polyethylene glycol was used to target the acidic pH of tumors. UV illumination, ethanol desolvation, oxygen bubbling, and a mixture of redox buffers were employed to prepare doxorubicin‐loaded HSA–LA nanoparticles. The nanocarrier was supposed to release the loaded doxorubicin in reductive and acidic pH media. Fourier‐transform infrared spectroscopy and energy dispersive X‐ray analysis indicated successful attachment of LA to HSA. The prepared nanoplatform presented improved doxorubicin loading efficiency and content and successfully released the loaded doxorubicin in the expected conditions. Protein corona study indicated that positively charged plasma proteins with molecular weights of nearly 80 kDa are absorbed to the surface of the nanoparticles. Furthermore, it showed desirable UV and storage stability, which implied its robustness and improved shelf life if applied in nanomedicine.

Nanotechnological Approaches to Enhance the Potential of α-Lipoic Acid for Application in the Clinic

“…They exhibit either a negative or a neutral charge under physiological pH conditions to prevent adsorption to serum proteins that can induce opsonization, complement activation, and rapid clearance. To achieve this feature, specific functional groups, such as the imidazole moiety and maleic anhydride [ 138 , 139 , 140 , 141 ], or coatings like polyethylene glycol, have been introduced [ 138 , 141 , 142 ]. Consequently, charge-reversible nanosystems exhibit enhanced plasma stability and can accumulate in tumour tissues.…”

Research progress of serum albumin in the field of drug delivery

“…69 The characteristics of tumor environment can be used to design selective and responsive vectors (Figure 3B) 70,71 with better therapeutic effects. 72 Liu et al 73 summarized that the responsive carriers mainly include pH response, REDOX response, enzyme response, ATP response, thermal response, ultrasonic response and magnetic response. The TME is characterized by high glutathione (GSH), high hydrogen peroxide (H 2 O 2 ), and acidic pH, which is conducive to cancer cell growth, invasion, and metastasis.…”

“…The antigen-specific T cells are then activated and proliferated, attacking the cells carrying the tumorspecific antigen, causing the tumor cells to die. 72,126 HSA nanocarriers are effectively absorbed by DC and exhibit additional cell activation and maturation, with therapeutic effects far exceeding those of nanocarriers carrying only a single drug.…”

“…Tumor cells have a specific microenvironment, which contains some special physiological signals, such as acidity, REDOX potential, special enzymes, reactive oxygen species, anoxic environment, etc (Figure 3C). 69 The characteristics of tumor environment can be used to design selective and responsive vectors (Figure 3B) 70,71 with better therapeutic effects 72 . Liu et al 73 summarized that the responsive carriers mainly include pH response, REDOX response, enzyme response, ATP response, thermal response, ultrasonic response and magnetic response.…”

A pH-Responsive Nanoplatform Based on Magnetic Mesoporous Silica Nanoparticles for Enhanced Treatment of Pancreatic Cancer

“…Doxorubicin (DOX) is a chemical drug which is widely used in the treatment of tumors, since it shows strong antitumor activity. − However, DOX also has serious limitations, including cardiotoxicity and multidrug resistance, which limit its potential clinical applications. , To overcome these problems, many nanocarrier systems have been designed to load DOX and achieve precise release in response to different stimulus response mechanisms, including pH, − enzyme activity, − oxidative stress, , photoresponsiveness, − etc. Polydopamine (PDA) is used as a “gatekeeper” because its solubility can be altered through protonation, which can facilitate the controlled release of DOX in acidic tumor environments. , In addition, PDA can also be spontaneously polymerized and coated onto various nanocarriers, thereby improving their stability and biocompatibility .…”