Wolf in Sheep’s Clothing: Taming Cancer’s Resistance with Human Serum Albumin? - Review

Sep 23, 2026

Uploaded by Patrick

Human serum albumin (HSA) is presented as a versatile nanocarrier for cancer drug delivery, with emphasis on countering chemotherapy resistance, particularly multidrug resistance type 1 (MDR1). The review analyzes cellular uptake of albumin-based nanoparticles and how chemical and surface modifications improve targeting to cancer cells and receptor engagement. It highlights established albumin receptors (gp60, gp18/30) and emerging targets (CD44, CD36, TfR1), and considers albumin dimer (dHSA) strategies. Clinical examples, including Abraxane and newer formulations (Pazenir, Fyarro for Sirolimus), are used to identify gaps and propose optimization strategies.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages33

Reading Time1 h 23 min

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International Journal of Nanomedicine Open Access Full Text Article REVIEW Wolf in Sheep’s Clothing: Taming Cancer’s Resistance with Human Serum Albumin? Iga Stukan 1 , Anna Żuk2 , Kamila Pukacka 3 , Julia Mierzejewska4 , Jakub Pawłowski4 , Bogusław Kowalski 4 , Maria Dąbkowska4 1Department of General Pathology, Pomeranian Medical University in Szczecin, Szczecin, Poland; 2Independent Laboratory of Community Pharmacy, Pomeranian Medical University in Szczecin, Szczecin, Poland; 3Department of Pharmaceutical Technology, Pomeranian Medical University in Szczecin, Szczecin, Poland; 4Independent Laboratory of Pharmacokinetic and Clinical Pharmacy, Pomeranian Medical University in Szczecin, Szczecin, Poland Correspondence: Maria Dąbkowska, Independent Laboratory of Pharmacokinetic and Clinical Pharmacy, Pomeranian Medical University in Szczecin, Szczecin, Poland, [Email maria.dabkowska@pum.edu.pl](Email maria.dabkowska@pum.edu.pl); Iga Stukan, Department of General Pathology, Pomeranian Medical University in Szczecin, Szczecin, Poland, Email [iga.stukan@pum.edu.pl](iga.stukan@pum.edu.pl) | Abstract: Human serum albumin (HSA) has emerged as a promising carrier for nanodrug delivery, offering unique structural properties that can be engineered to overcome key challenges in cancer treatment, especially resistance to chemotherapy. This review focuses on the cellular uptake of albumin-based nanoparticles and the modifications that enhance their ability to bypass resistance mechanisms, particularly multidrug resistance type 1 (MDR1), by improving targeting to cancer cells. In our unique approach, we integrate the chemical properties of albumin, its interactions with cancer cells, and surface modifications of albumin-based delivery systems that enable to bypass resistance mechanisms, particularly those related to MDR1, and precisely target receptors on cancer cells to improve treatment efficacy. We discuss that while well-established albumin receptors such as gp60 and gp18/30 are crucial for cellular uptake and transcytosis, their biology remains underexplored, limiting their translational potential. Additionally, we explore the potential of emerging targets, such as cluster of differentiation 44 (CD44), cluster of differentiation (CD36) and transferrin receptor TfR1, as well as the advantages of using dimeric forms of albumin (dHSA) to further enhance delivery to resistant cancer cells. Drawing from clinical examples, including the success of albumin-bound paclitaxel (Abraxane) and new formulations like Pazenir and Fyarro (for Sirolimus), we identify gaps in current knowledge and propose strategies to optimize albumin-based systems. In conclusion, albumin-based nanoparticles, when tailored with appropriate modifications, have the potential to bypass multidrug resistance and improve the targeting of cancer cells. By enhancing albumin’s ability to efficiently deliver therapeutic agents, these carriers represent a promising approach to addressing one of oncology’s most persistent challenges, with substantial potential to improve cancer treatment outcomes.
Keywords: HSA, drug delivery system, drug resistance, nanomedicine, gp60, HSA dimer, pazenir, fyarro, abraxane | | --- | | Introduction
Human serum albumin (HSA) is among the most extensively studied carriers in cancer therapy because of its unique characteristics, such as biocompatibility and biodegradability.1 Albumin is also actively scavenged by cancer cells due to its high capacity for fatty acid binding and its glutamine content, which makes up approximately 10% of its amino acid composition. This makes albumin a valuable source for fueling the Krebs cycle and lipid biosynthesis, as well as providing nitrogen necessary for amino acid and nucleotide synthesis.2–7 Interestingly, hypoalbuminemia in cancer is frequently associated with cancer chemoresistance due to reduced drug transportation (reviewed in) .8
Albumin structure is amenable to modifications, also allo

FAQs

How does human serum albumin (HSA) help deliver nanodrugs in cancer therapy?

HSA is highlighted as a biocompatible and modifiable carrier with favorable structural properties. The review emphasizes its use to engineer cellular uptake and improve delivery to cancer cells.

Which resistance mechanism is especially targeted in this review?

The focus is on bypassing chemotherapy resistance mechanisms, with particular attention to multidrug resistance type 1 (MDR1).

What receptor targets are discussed to improve albumin nanoparticle uptake and targeting?

The review discusses well-established albumin receptors such as gp60 and gp18/30, and also explores emerging targets including CD44, CD36, and the transferrin receptor TfR1.

Sep 23, 2026

Uploaded by Patrick