Emerging Albumin-Binding Anticancer Drugs for Tumor-Targeted Drug Delivery: Current Understandings and Clinical Translation

Abstract

Albumin has shown remarkable promise as a natural drug carrier by improving pharmacokinetic (PK) profiles of anticancer drugs for tumor-targeted delivery. The exogenous or endogenous albumin enhances the circulatory half-lives of anticancer drugs and passively target the tumors by the enhanced permeability and retention (EPR) effect. Thus, the albumin-based drug delivery leads to a potent antitumor efficacy in various preclinical models, and several candidates have been evaluated clinically. The most successful example is Abraxane, an exogenous human serum albumin (HSA)-bound paclitaxel formulation approved by the FDA and used to treat locally advanced or metastatic tumors. However, additional clinical translation of exogenous albumin formulations has not been approved to date because of their unexpectedly low delivery efficiency, which can increase the risk of systemic toxicity. To overcome these limitations, several prodrugs binding endogenous albumin covalently have been investigated owing to distinct advantages for a safe and more effective drug delivery. In this review, we give account of the different albumin-based drug delivery systems, from laboratory investigations to clinical applications, and their potential challenges, and the outlook for clinical translation is discussed. In addition, recent advances and progress of albumin-binding drugs to move more closely to the clinical settings are outlined.

Albumin-Modified Gold Nanoparticles as Novel Radiosensitizers for Enhancing Lung Cancer Radiotherapy

“…Their accumulation in the tumors can be attributed to the effective interaction of albumin with gp60 receptor and SPARC, which promotes the local concentration of loaded albumin nanocarriers in tumors while providing nutrients and energy to facilitate the rapid proliferation of tumor cells. 34 , 50 , 51 In addition, some research also suggests that Alb-NPs might act as an inducer of Alb-binding protein aggregation due to their ability to bind and cross-link to multiple receptors. 34 Therefore, the Alb-modified nanoplatform exhibits good tumor-targeted drug delivery.…”

Peptide-Based Bioconjugates and Therapeutics for Targeted Anticancer Therapy

“…In addition, various strategies have been introduced, such as a method to increase blood stability and the targeting effect using other proteins, including albumin or globulin. In particular, an albumin-based peptide delivery system can enhance peptide stability within the circulation, leading to enhanced antitumor efficacy [ 32 ]. The main purpose of using nanotechnology or carriers with peptides is to overcome blood stability issues, which are a fundamental problem for peptide-based molecules, meaning that many nano- or carrier-based drug candidates are currently being evaluated for conversion from laboratory investigations to clinical applications.…”

Investigating the Interaction of an Anticancer Nucleolipidic Ru(III) Complex with Human Serum Proteins: A Spectroscopic Study

“…Since anticancer Ru(III)-based compounds are usually administered intravenously, extensive in vivo binding to plasma proteins can have significant consequences on the biodistribution and bioavailability of these complexes [ 57 ]. These proteins can in fact behave as suitable carriers for ruthenium inside cells through permeation and/or endocytosis mechanisms, providing selective tumor targeting [ 58 , 59 , 60 , 61 , 62 ].…”

“…In detail, human serum albumin (HSA) is the major soluble protein constituent of the circulatory system, identified as a well-established transporter of both endogenous and exogenous species in the bloodstream, including drugs [ 63 , 64 ]. In addition, HSA is known to accumulate in tumors as a consequence of enhanced permeability and retention effect [ 60 , 61 , 62 ].…”