Design, strategies, and therapeutics in nanoparticle-based siRNA delivery systems for breast cancer.

Utilizing small interfering RNA (siRNA) as a treatment for cancer, a disease largely driven by genetic aberrations, shows great promise. However, implementing siRNA therapy in clinical practice is challenging due to its limited bioavailability following systemic administration. An attractive approach to address this issue is the use of a nanoparticle (NP) delivery platform, which protects siRNA and delivers it to the cytoplasm of target cells. We provide an overview of design considerations for using lipid-based NPs, polymer-based NPs, and inorganic NPs to improve the efficacy and safety of siRNA delivery. We focus on the chemical structure modification of carriers and NP formulation optimization, NP surface modifications to target breast cancer cells, and the linking strategy and intracellular release of siRNA. As a practical example, recent advances in the development of siRNA therapeutics for treating breast cancer are discussed, with a focus on inhibiting cancer growth, overcoming drug resistance, inhibiting metastasis, and enhancing immunotherapy.

In-situ re-melting and re-solidification treatment of selective laser sintered polycaprolactone lattice scaffolds for improved filament quality and mechanical properties.

Selective laser sintering (SLS) is a promising additive manufacturing technique that produces biodegradable tissue-engineered scaffolds with highly porous architectures without additional supporting. However, SLS process inherently results in partially melted microstructures which significantly impair the mechanical properties of the resultant scaffolds for potential applications in tissue engineering and regenerative medicine. Here, a novel post-treatment strategy was developed to endow the SLS-fabricated polycaprolactone (PCL) scaffolds with dense morphology and enhanced mechanical properties by embedding them in dense NaCl microparticles for in-situ re-melting and re-solidification. The effects of re-melting temperature and dwelling time on the microstructures of the SLS-fabricated filaments were studied. The results demonstrated that the minimum requirements of re-melting temperature and dwelling time for sufficient treatment were 65 °C and 5 min respectively and the size of the SLS-fabricated filaments was reduced from 683.3 ± 28.0 µm to 601.6 ± 17.4 µm. This method was also highly effective in treating three-dimensional (3D) PCL lattice scaffolds, which showed improved filament quality and mechanical properties after post-treatment. The treated PCL scaffolds with an initial compressive modulus and strength of 3027.8 ± 204.2 kPa and 208.8 ± 14.5 kPa can maintain their original shapes after implantation in vivo for 24 weeks. Extensive newly-grown tissues were found to gradually penetrate into the porous regions along the PCL filaments. Although degradation occurred, the mechanical properties of the implanted constructs stably maintained. The presented method provides an innovative, green and general post-treatment strategy to improve both the filament quality and mechanical properties of SLS-fabricated PCL scaffolds for various tissue engineering applications.

Lymphatic-targeted therapy following neoadjuvant chemotherapy: a promising strategy for lymph node-positive breast cancer treatment.

Neoadjuvant chemotherapy has been increasingly used to downstage breast cancer prior to surgery recently. However, in some cases, it was observed that despite sufficient regression of primary tumors, the metastatic lymph nodes remained nonresponsive. In this study, we applied lymphatic-targeted strategy to evaluate its efficacy and safety for patients presenting refractory nodes following systemic chemotherapy. A total of 318 breast cancer patients were demonstrated with lymph node metastasis by needle biopsy and given neoadjuvant chemotherapy. Two cycles later, 72 patients were observed with responsive tumors but stable nodes, 42 of which received a subcutaneous injection of lymphatic-targeted pegylated liposomal doxorubicin during the third cycle, while the remaining 30 patients were continued with former neoadjuvant therapeutic pattern and regarded as the control. Lymphatic-targeted treatment substantially increased both clinical and pathological node response rate [62 % (26/42) vs. 13 % (4/30) and 12 % (5/42) vs. 0 (0/30), respectively], and induced a higher apoptosis level of metastatic cells (median, 41 vs. 6 %), compared with the control. Moreover, a higher disease-free survival was observed after a median follow-up of 4 years (69 vs. 56 %). Inflammatory reaction surrounding injection sites was the most common side effect. Lymphatic chemotherapy has reliable efficacy and well-tolerated toxicity for breast cancer patients presenting refractory lymph nodes following neoadjuvant chemotherapy.