Paclitaxel (PTX) is a chemotherapeutic agent which shows antitumor activities against a broad spectrum of cancers. Yet, the current formulation of PTX used in clinic may cause a number of adverse reactions, which significantly limit its application. To obtain better clinical use of PTX, we report, for the first time, iRGD‐PTX conjugate nanoparticles (NPs) for targeted PTX delivery. iRGD‐PTX conjugate was synthesized from thiolated iRGD and 6‐maleimidocaproic acid‐PTX through Michael addition reaction. iRGD‐PTX NPs with hydrodynamic diameter of ~110 nm were self‐assembled from iRGD‐PTX conjugate in deionized water. The as‐prepared iRGD‐PTX NPs exhibit good stability in phosphate buffered saline (PBS) buffer and fetal bovine serum containing PBS buffer. iRGD‐PTX NPs exhibit sustained drug release behaviors. The in vitro studies show that iRGD‐PTX NPs can be internalized by 4T1 cells by integrin αV‐mediated endocytosis, resulting in better in vitro antitumor activity as compared to free PTX. The in vivo studies demonstrate that iRGD‐PTX NPs exhibit enhanced tumor accumulation. The iRGD‐PTX NPs reported here represent a novel PTX nanoplatform to achieve targeted PTX delivery.

Dimethylcurcumin (ASC−J9, DMC), a newly developed anti‐AR agent, suppresses androgen receptor (AR) signaling pathways by degradation of full‐length and splice variant of ARs, showing efficient growth inhibition effect on castration‐resistant prostate cancer (PCa). However, DMC is extremely hydrophobic, which significantly limits its applications. Here, we developed DMC‐loaded methoxylpoly (ethylene glycol)‐retinoic acid (DMC@mPEG2000‐RA) micelles in order to improve the solubility of DMC and its effect on growth inhibition of castration‐resistant PCa. DMC@mPEG2000‐RA micelles with hydrodynamic diameter around 200 nm and drug loading content of 6.0% were prepared by thin film hydration‐ultrasonic method. The as prepared micelles show good colloidal stability in PBS buffer and 10% FBS containing PBS buffer. The in vitro drug release study shows that DMC@mPEG2000‐RA micelles exhibit initially relative fast drug release followed by sustained drug release behaviors. The cellular uptake study reveals that the cellular uptake amount of DMC@mPEG2000‐RA micelles is significantly higher than that of free DMC and caveolae plays important roles in cellular uptake of DMC@mPEG2000‐RA micelles. Finally, DMC@mPEG2000‐RA micelles exhibit significantly enhanced in vitro antitumor activity against C4‐2 and 22Rv1 cells as compared to free DMC. DMC@mPEG2000‐RA micelles were proved to be an efficient formulation of DMC for suppression of castration‐resistant PCa.

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