TPGS/hyaluronic acid dual-functionalized PLGA nanoparticles delivered through dissolving microneedles for markedly improved chemo-photothermal combined therapy of superficial tumor.

Nanoparticles (NPs) have shown potential in cancer therapy, while a single administration conferring a satisfactory outcome is still unavailable. To address this issue, the dissolving microneedles (DMNs) were developed to locally deliver functionalized NPs with combined chemotherapy and photothermal therapy (PTT). α-Tocopheryl polyethylene glycol succinate (TPGS)/hyaluronic acid (HA) dual-functionalized PLGA NPs (HD10 NPs) were fabricated to co-load paclitaxel and indocyanine green. HD10 NPs significantly enhanced the cytotoxicity of low-dose paclitaxel because of active and mitochondrial targeting by HA and TPGS, respectively. PTT could further sensitize tumor cells toward chemotherapy by promoting apoptosis into the advanced period, highly activating caspase 3 enzyme, and significantly reducing the expression of survivin and MMP-9 proteins. Further, the anti-tumor effects of HD10 NPs delivered through different administration routes were conducted on the 4T1 tumor-bearing mice. After a single administration, HD10 NPs delivered with DMNs showed the best anti-tumor effect when giving chemotherapy alone. As expected, the anti-tumor effect was profoundly enhanced after combined therapy, and complete tumor ablation was achieved in the mice treated with DMNs and intra-tumor injection. Moreover, DMNs showed better safety due to moderate hyperthermia. Therefore, the DMNs along with combined chemo-photothermal therapy provide a viable treatment option for superficial tumors.

Novel functionalization strategies of polymeric nanoparticles as carriers for brain medications.

For targeted brain delivery, nanoparticles (NPs) should bypass the blood-brain barrier (BBB). Novel functionalization strategies, based on low-density lipoprotein receptor (LDLR) binding domain, have been here tested to increase the brain targeting efficacy of poly d,l-lactic-co-glycolic acid (PLGA) NPs, biodegradable and suited for biomedical applications. Custom-made PLGA NPs were functionalized with an apolipoprotein E modified peptide (pep-apoE) responsible for LDLR binding, or with lipocalin-type prostaglandin-d-synthase (L-PGDS), highly expressed in the brain. At the comparison of pep-apoE and L-PGDS sequences, a highly homologs region was here identified, indicating that also L-PGDS could bind LDLR. Non-functionalized and functionalized NPs did not affect the viability of cultured human dendritic cells, protagonists of the immune response, and did not activate them to a proinflammatory profile. At 2 h after intravenous injection in mice, functionalized, but not the non-functionalized ones, fluorescent-tagged NPs were observed in the cerebral cortex parenchyma. The NPs were mostly internalized by neurons and microglia; glial cells showed a weak activation. The findings indicate that the tested functionalization strategies do not elicit adverse immune responses and that the peptidic moieties enable BBB traversal of the NPs, thus providing potential brain drug carriers. These could be especially effective for brain diseases in which LDLR is involved. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 847-858, 2017.

TPGS/hyaluronic acid dual-functionalized PLGA nanoparticles delivered through dissolving microneedles for markedly improved chemo-photothermal combined therapy of superficial tumor

Nanoparticles (NPs) have shown potential in cancer therapy, while a single administration conferring a satisfactory outcome is still unavailable. To address this issue, the dissolving microneedles (DMNs) were developed to locally deliver functionalized NPs with combined chemotherapy and photothermal therapy (PTT).