RESUMO
Several therapeutic nanosystems have been engineered to remedy the shortcomings of cancer monotherapies, including immunotherapy (stimulating the host immune system to eradicate cancer), to improve therapeutic efficacy with minimizing off-target effects and tumor-induced immunosuppression. Light-activated components in nanosystems confer additional phototherapeutic effects as combinatorial modalities; however, systemic and thermal toxicities with unfavorable accumulation and excretion of nanoystem components now hamper their practical applications. Thus, there remains a need for optimal multifunctional nanosystems to enhance targeted, durable, and mild combination therapies for efficient cancer treatment without notable side effects. Methods: A nanosystem constructed with a base core (poly-L-histidine [H]-grafted black phosphorus [BP]) and a shell (erythrocyte membrane [EM]) is developed to offer a mild photoresponsive (near-infrared) activity with erythrocyte mimicry. In-flight electrostatic tailoring to extract uniform BP nanoparticles maintains a hydrodynamic size of <200 nm (enabling enhanced permeability and retention) after EM cloaking and enhances their biocompatibility. Results: Ephrin-A2 receptor-specific peptide (YSA, targeting cancer cells), interleukin-1α silencing small interfering RNA (ILsi, restricting regulatory T cell trafficking), and paclitaxel (X, inducing durable chemotherapeutics) are incorporated within the base core@shell constructs to create BP-H-ILsi-X@EM-YSA architectures, which provide a more intelligent nanosystem for combination cancer therapies. Conclusion: The in-flight tailoring of BP particles provides a promising base core for fabricating <200 nm EM-mimicking multifunctional nanosystems, which could be beneficial for constructing smarter nanoarchitectures to use in combination cancer therapies.
Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Nanopartículas/química , Neoplasias Experimentais/terapia , Paclitaxel/administração & dosagem , Fósforo/química , Terapêutica com RNAi/métodos , Animais , Antineoplásicos Fitogênicos/uso terapêutico , Linhagem Celular Tumoral , Membrana Celular/química , Terapia Combinada/métodos , Eritrócitos/química , Histidina/química , Interleucina-1alfa/genética , Interleucina-1alfa/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Nanopartículas/efeitos adversos , Neoplasias Experimentais/tratamento farmacológico , Paclitaxel/uso terapêuticoRESUMO
In this study, the effects of the aqueous extract of Anemarrhena rhizome on cell proliferation and neuropeptide Y expression in the dentate gyrus of streptozotocin-induced diabetic rats were investigated via immunohistochemistry for 5-bromo-2'-deoxyuridine (BrdU) and neuropeptide Y. The results showed that the treatment with 50 to 200 microg/kg/day for 7 days of the aqueous extract of Anemarrhena rhizome increased new cell formation and neuropeptide Y expression in the dentate gyrus of diabetic rats reduced by the treatment with streptozotocin in rat.