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Background: Micellization provides numerous merits for the delivery of water insoluble anti-cancer therapeutic agents including a nanosized ‘core–shell’ drug delivery system. Recently, hydrophobically-modified polysaccharides and proteins are attracting much attention as micelle forming polymers to entrap poorly soluble anti-cancer drugs. Method: By virtue of their small size, the self-assembled micelles can passively target tumor tissues via enhanced permeation and retention effect (EPR). Moreover, the amphiphilic micelles can be exploited for active-targeted drug delivery by attaching specific targeting ligands to the outer micellar hydrophilic surface. Results: Here, we review the conjugation techniques, drug loading methods, physicochemical characteristics of the most important amphiphilic polysaccharides and proteins used as anti-cancer drug delivery systems. Attention focuses on the mechanisms of tumor-targeting and enhanced anti-tumor efficacy of the encapsulated drugs. This review will highlight the remarkable advances of hydrophobized polysaccharide and protein micelles and their potential applications as anti-cancer drug delivery nanosystems. Conclusion: Micellar nanocarriers fabricated from amphiphilic natural polymers hold great promise as vehicles for anti-cancer drugs.

Breast cancer is the most global dominant cancer among females. Although there are continuously growing strategies to develop new therapies, the outcomes are usually insufficient. Simultaneous combinational therapy using more than one drug is a promising strategy to treat breast cancer. Yet, administration of these drugs in their free form is usually associated with diverse side effects. Nanoencapsulation can afford entrapping drugs within the same nanocarrier for enhanced effect. Protein micelles have been widely utilized in nanoencapsulation owing to their biocompatibility and stability. In this study, dasatinib (DAS) and celecoxib (CXB) were co-encapsulated in the hydrophobic inner core of sodium caseinate micelles via a facile encapsulation method. In vitrocytotoxicity study for the prepared micelles was conducted on MCF-7 (hormone sensitive) and MDA-MB-231 (Triple negative) human breast cancer cell lines to evaluate their anti-cancer effect. Furthermore, the antitumor efficacy and the toxicity of the prepared micelles were examined in breast cancer animal model. Dual drug-loaded micelles revealed improved cytotoxic and synergistic effect against the examined cancer cell lines when compared to free drugs combination. More importantly, in vivostudies demonstrated enhanced antitumor effect with increased apoptosis, reduced angiogenesis, proliferation and migration. In addition, this nanoplatform was found to minimize the cytotoxic effects of both DAS and CXB. In conclusion, utilization of DAS/CXB-loaded sodium caseinate micelles can act as a promising drug delivery platform with increased drugs sensitization and minimized toxicity.