Folic acid receptor-targeted human serum albumin nanoparticle formulation of cabazitaxel for tumor therapy

Abstract

BackgroundWe previously developed cabazitaxel (CTX)-loaded human serum albumin nanoparticles (NPs-CTX) via a self-assembly method, and these NPs showed efficacy in prostate cancer therapy. Many studies have shown that the levels of folic acid (FA) receptor on the surface of various tumor cells are high. Therefore, FA-modified NPs-CTX may have enhanced antitumor effects compared with unmodified NPs-CTX.MethodsNPs-CTX were first prepared via self-assembly, and FA was conjugated on the surface of NPs-CTX through the -NH2 groups of the NPs to produce FA-NPs-CTX. The FA-NPs-CTX were evaluated in tumor cells with high FA receptor (FR) expression in vitro and in vivo.ResultsBoth NPs-CTX and FA-NPs-CTX exhibited good stability and morphology. Drug release from the NPs was not affected by FA conjugation. Compared with CTX dissolved in a mixture of Tween 80 and 13% ethanol (w/w) at a ratio of 1:4 (v/v) (Tween-CTX), the two nanoformulations had lower lytic activity against normal red blood cells. However, FA-NPs-CTX showed greater inhibition of tumor cells with overexpressed FR, compared with NPs-CTX, in the cytotoxicity experiments. Moreover, the cellular uptake of FA-NPs-CTX was enhanced through FR-mediated endocytosis in HeLa cells in vitro and HeLa xenograft tumors in vivo. Although Tween-CTX exhibited tumor growth inhibition similar to FA-NPs-CTX in vivo, this inhibition also caused adverse side effects; the median lethal dose (LD50) of Tween-CTX to mice was 5.68 mg/kg, while FA-NPs-CTX-treated mice survived at doses exceeding 400 mg/kg.ConclusionThe results showed that FA-NPs-CTX caused inhibition of tumor growth in a manner similar to that of Tween-CTX; however, the safety and tolerability of CTX were greatly improved by FA conjugation compared with those of Tween-CTX. In summary, FA-NPs-CTX have great potential in CTX delivery, and this formulation is a promising candidate for the treatment of cancers with high FR levels.

A Smart Multifunctional Nanoparticle for Enhanced Near-Infrared Image-Guided Photothermal Therapy Against Gastric Cancer

“…For instance, specific cell surface receptors, such as transferrin or folate receptors, are overexpressed in tumor cells such as malignant glioma and breast cancer. 33 Nanomaterials modified with peptides, aptamers, and monoclonal antibodies 30 , 33 can increase specific cellular uptake through receptor-mediated endocytosis (RME) effect, thus resulting in the accumulation of drugs in the target cells and increasing the payload of drug delivery. Integrins are a family of transmembrane receptors capable of mediating bidirectional signaling through the membrane, including invasion, migration, survival, and proliferation.…”

The Wnt non-canonical signaling modulates cabazitaxel sensitivity in prostate cancer cells

“…Furthermore, the promising therapeutic findings on Cab benefits (as mono-or combined therapies) in other types of cancers such as cisplatin-resistant germ cell tumor cells [16], breast cancer [17,18], sorafenib-resistant hepatocellular carcinomas [19], mCRPCa [20,21], cytarabine-resistant leukemia [22], glioblastoma [23] or gliomas [24] impel for more studies to understand Cab modes of action. Furthermore, the current growing interest in developing Cab-carrying nanovehicles (liposomes, micelles, and nanoparticles) to reduce Cab's side effects and increase its delivery and efficacy [17,18,[25][26][27][28][29][30][31][32][33][34] urges again for more investigations on Cab.…”

Inhibition of Glycation-Induced Aggregation of Human Serum Albumin by Organic–Inorganic Hybrid Nanocomposites of Iron Oxide-Functionalized Nanocellulose

“…8,9 Albumin proteins such as HSA and bovine serum albumin play important roles as carrier proteins and bind with endogenous and exogenous ligands including fatty acids, hormones, metal ions, small molecules, drugs, and so on. 10,11 Destabilization of the native structure of proteins is responsible for many diseases and can be favored by a change in pH, high temperature, electrostatic interactions, presence of salts, surfactants, and metal ions, change in osmolyte concentration, high pressure, ionic strength, and so on, which may result in the formation of misfolded intermediates, which are otherwise inaccessible under normal physiological conditions. 12−15 The formation of partially unfolded or destabilized structures ultimately results in the formation of aggregated proteins.…”