Recent Advances on the Development of Pharmacotherapeutic Agents on the Basis of Human Serum Albumin

Abstract

Human serum albumin (HSA), a major transport protein component in blood plasma, has been reported recently to play many important roles in pharmacotherapeutics development. Owing to its promising intrinsic binding capability of drug molecules, HSA offers favorable characteristics and can be directly used as its monomeric formula or can be fabricated into protein based nanoparticle platforms to realize the effective delivery of therapeutic molecules into targeted diseases areas. In addition, HSA can also serve as a protein stabilizer or environment-responsive moieties to hybridize with the functional materials including polymers or inorganic nanoparticles through the covalent reactions or electrostatic interactions, and can thus greatly alter the relevant biological distribution and pharmacokinetic behavior to improve their therapeutic efficacy. By right, extensive studies have been conducted to develop HSA-conjugated pharmacotherapeutic agents toward effective in vitro and in vivo diseases diagnosis and treatment. The current review gives an in-detail account of the latest progresses of HSA-based carriers as functional protein materials, mainly with respect to its conjugation types, formulation aspects, and importantly their promising applications towards enhanced drug delivery and medical diagnosis.

Design of protein homocystamides with enhanced tumor uptake properties for 19F magnetic resonance imaging

“…[1][2][3][4][5][6][7][8][9] By encapsulating drugs or genes either in its monomeric or nanoparticle formula, HSA has significantly improved the therapeutic efficacy of agents against a variety of human diseases including neutropenia, hemostasis, substance abuse, and oncology. may permit quantification and characterization of the catabolic processes in vivo, 35 which could not be achieved with conventional radiolabels and fluorescent labels.…”

Development of the application of speciation in chemistry

“…Based on their enhanced permeability and retention due to the accumulation of HSA in tumor tissues, Pt(IV) prodrugs were designed to bind non-covalently to native HSA by Lippard et al [174], and thus the controlled release of these compounds is possible in disease areas [175,176]. Maleimide-functionalized compounds have also been developed (including Pt(IV) complexes [177]) that can bind covalently to the free thiol group of HSA (Cys34), although a cleavable specific bond between the drug and maleimide moieties is beneficial in these cases, e.g., an acidic environment sensitive linker [176].…”

“…Maleimide-functionalized compounds have also been developed (including Pt(IV) complexes [177]) that can bind covalently to the free thiol group of HSA (Cys34), although a cleavable specific bond between the drug and maleimide moieties is beneficial in these cases, e.g., an acidic environment sensitive linker [176]. macrochelate [183], and logK HSA = 3.88 and 4.17 were reported for cisplatin and oxaliplatin, respectively, by Rudnev et al [182].…”

‘Smartening’ anticancer therapeutic nanosystems using biomolecules

“…For instance, albumin [5,6], ferritin [7], and small heat shock proteins [8] have already been used for this purpose, the latter two forming hollow structures (nanocages) where cargoes can be encapsulated. Proteins can be modified chemically with ease, which facilitates their attachment to therapeutic agents and other building blocks of STNS [9,10].…”

“…Although polyethylene glycol (PEG) is traditionally used for this [23], biomolecules constitute another valuable source of anti-fouling agents. For instance, albumin has been used to decorate the surface of NPs with stealth purposes [5,24]. Similarly, recombinant CD47 protein, which is a 'marker of self' in mammalian red blood cells, has been grafted on the surface of NPs to increase their circulation half-life and accumulation in tumors [25].…”