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Satisfactory drug loading capacity and stability are the two main factors that determine the anti-cancer performance. In general, the stability of the micelles is reduced when the drug loading (DL) is increased. Therefore, it was a challenge to have high drug loading capacity and good stability. In this study, we introduced a hydrophilic poly (L-Lysine) (PLL) segment with different molecular-weights into the monomethoxy poly (ethylene glycol)-poly (D, L-lactide) (MPEG-PDLLA) block copolymer to obtain a series of novel triblock MPEG-PDLLA-PLL copolymers. We found that the micelles formed by a specific MPEG2k-PDLLA4k-PLL1k copolymer could encapsulate docetaxel (DTX) with a satisfactory loading capacity of up to 20% (w/w) via the thin film hydration method, while the stability of drug loaded micellar formulation was still as good as that of micelles formed by MPEG2k-PDLLA1.7k with drug loading of 5% (w/w). The results from computer simulation study showed that compared with MPEG2k-PDLLA1.7k, the molecular chain of MPEG2k-PDLLA4k-PLL1k could form a more compact funnel-shaped structure when interacted with DTX. This structure favored keeping DTX encapsulated in the copolymer molecules, which improved the DL and stability of the nano-formulations. The in vitro and in vivo evaluation showed that the DTX loaded MPEG2k-PDLLA4k-PLL1k (DTX/MPEG2k-PDLLA4k-PLL1k) micelles exhibited more efficiency in tumor cell growth inhibition. In conclusion, the MPEG2k-PDLLA4k-PLL1k micelles were much more suitable than MPEG2k-PDLLA1.7k for DTX delivery, and then the novel nano-formulations showed better anti-tumor efficacy in breast cancer therapy.

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A facile and general coordination-precipitation method is developed to synthesize insoluble metal Roussin's black salts (Me-RBSs) as a new type of NIR-responsive NORMs. The weak-field ligand coordination of metal-RBS brings a NIR absorption effect of Me-RBSs, and further gives rise to the NIR adsorption-dependent NIR-responsive NO release profile. Intratumoral NIR-responsive release of NO effectively inhibits the growth and metastasis of the metastatic breast cancer. Aqueous insolubility of Me-RBSs ensures lower cytotoxicity and higher thermostability compared with traditional soluble RBSs. This work establishes a new class of NIR-sensitive NO donors, and may spark new inspiration for designing intelligent gas-releasing molecules.

Currently, epidermoid cancer is one of the most common malignancies among Caucasians. Traditional treatment may yield uncomfortable side effects for the patient. In order to solve these problems, the authors develop a near-infrared (NIR) responsive PEGylated gold nanorod (GNR-PEG) and doxorubicin (DOX) loaded dissolvable hyaluronic acid (HA) microneedle (GNR-PEG&DOX@HA MN) for human epidermoid cancer therapy. The as-made GNR-PEG&DOX@HA MNs has good skin penetration capability and heating ability. The heating can be transferred to the center of the tumor sites and the temperature is shown to rise up to 60°C within 5 min. Meanwhile, the release behavior of the DOX from GNR-PEG&DOX@HA MNs can be controlled by NIR light. The GNR-PEG&DOX@HA MNs shows good cell inhibition, and the photothermal effect is shown to completely destroy A431 cells in vitro. For in vivo antitumor study, the group treated with GNR-PEG&DOX@HA MNs transcutaneously reveals a remarkable antitumor efficacy, such that all mice are cured without recurrence under only one treatment. Hence, this novel transdermal drug delivery strategy offers hope to human epidermoid cancer therapy, and GNR-PEG&DOX@HA MN may serve as a promising candidate in clinical translation for human epidermoid cancer therapy.

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In this study we employed self-designed PDLLA-PEG-PDLLA (PLEL) thermosensitive hydrogel to blend with norcantharidin (NCTD), a hydrophilic chemotherapeutic drug possessing curative effect on primary hepatocellular carcinoma (HCC) and adverse effects, then utilized the composite in HCC interstitial chemotherapy. PLEL copolymer was synthesized by ring-opening polymerization, NCTD-loaded PLEL hydrogel was prepared in a simple and reasonable way. The addition of NCTD had no significant effect on the temperature-dependent rheological properties of PLEL hydrogel. The pH values of NCTD-loaded gel solutions (13 wt%) and free NCTD solutions with three drug concentrations of 0.4 mg/mL, 0.8 mg/mL and 1.2 mg/mL under different storage conditions met the pH requirement of small-volume injection. There was no significant difference among the drug release behaviors of NCTD-loaded gels with drug concentrations of 0.4 mg/mL, 0.8 mg/mL and 1.2 mg/mL, they fitted first-order dynamics, exhibited significantly slower drug release than free drug solutions and the release was mainly based on drug diffusion. Drug-loaded gel solution (13 wt%) could evenly distribute throughout tumor tissue before converting into gel after being intratumorally injected and was able to significantly prolong retention time of the drug in tumor compared to free drug solution. The sustained-release performance of NCTD-loaded gel (13 wt%) was confirmed from the perspective of pharmacodynamics in vitro. The in vivo evaluation demonstrated that intratumoral injection of NCTD-loaded PLEL gel (13 wt%) was capable of improving curative effect of the drug and reducing its toxicity.