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Abstract Malignant bone tumors associated with aggressive osteolysis are currently hard to be cured by the clinical strategies. Nevertheless, nanomedicine might provide a promising therapeutic opportunity. Here, we developed a multifunctional melanin-like nanoparticle for bone-targeted chemo-photothermal treatment of malignant bone tumors. The particle was originally fabricated from alendronate-conjugated polydopamine nanoparticle (PDA-ALN) that exhibited excellent photothermal effect and high affinity to hydroxyapatite. PDA/Fe-ALN significantly enhanced the magnetic resonance contrast of the bone tumors in vivo , suggesting that more PDA-ALN accumulated at the osteolytic bone lesions in the tumors compared with the non-targeting PDA. Chemodrug SN38 was efficiently loaded on PDA-ALN, and the drug release could be triggered by near-infrared irradiation and acidic stimulus. Finally, the combined chemo-photothermal therapy efficiently suppressed the growth of bone tumors and reduced the osteolytic damage of bones at a mild temperature around 43 °C. This study provides an efficient and robust nanotherapeutics for the treatment of malignant bone tumors. [ABSTRACT FROM AUTHOR]

The treatment of bone tumors is a challenging problem due to the inefficient delivery of therapeutics to bone and the bone microenvironment-associated tumor resistance to chemo- and radiotherapy. Here, we developed a bone-targeted nanoparticle, aspartate octapeptide-modified dendritic platinum-copper alloy nanoparticle (Asp-DPCN), for photothermal therapy (PTT) of bone tumors. Asp-DPCN showed much higher affinity toward hydroxyapatite and bone fragments than the non-targeted DPCN in vitro . Furthermore, Asp-DPCN accumulated more efficiently around bone tumors in vivo , and resulted in a higher temperature in bone tumors during PTT. Finally, Asp-DPCN-mediated PTT not only efficiently depressed the tumor growth but also significantly reduced the osteoclastic bone destruction. Our study developed a promising therapeutic approach for the treatment of bone tumors. [ABSTRACT FROM AUTHOR]

Design of an efficient gene vector based on dendrimer remains a great challenge due to the presence of multiple barriers in gene delivery. Single-functionalization on dendrimer cannot overcome all the barriers. In this study, we synthesized a list of single-, dual- and triple-functionalized dendrimers with arginine, phenylalanine and histidine for gene delivery using a one-pot approach. The three amino acids play different roles in gene delivery: arginine is essential in formation of stable complexes, phenylalanine improves cellular uptake efficacy, and histidine increases pH-buffering capacity and minimizes cytotoxicity of the cationic dendrimer. A combination of these amino acids on dendrimer generates a synergistic effect in gene delivery. The dual- and triple-functionalized dendrimers show minimal cytotoxicity on the transfected NIH 3T3 cells. Using this combination strategy, we can obtain triple-functionalized dendrimers with comparable transfection efficacy to several commercial transfection reagents. Such a combination strategy should be applicable to the design of efficient and biocompatible gene vectors for gene delivery. [ABSTRACT FROM AUTHOR]

Photothermal-chemotherapy (PT-CT) is a promising strategy for cancer treatment, but its development is hindered by the issues regarding to the long-term safety of carriers and imperfect drug release profiles. In this article, we use polyethylene glycol-modified polydopamine nanoparticles (PDA-PEG) as an outstanding PT-CT agent for cancer treatment. PDA-PEG possesses excellent biocompatibility and photothermal effect, and could easily load anticancer drugs such as doxorubicin (DOX) and 7-ethyl-10-hydroxycamptothecin (SN38) via π-π stacking and/or hydrogen binding. Moreover, the drug-loaded PDA-PEG showed great stability and drug-retaining capability in physiological condition, and could respond to multiple stimuli including near infrared light, pH and reactive oxygen species to trigger the release of loaded anticancer drugs. The in vitro and in vivo studies demonstrated that PDA-PEG-mediated PT-CT showed synergetic effect for cancer therapy. [ABSTRACT FROM AUTHOR]

Abstract The design of efficient and universal carriers to transport proteins into cells is highly desirable in the development of biotherapeutics. However, intracellular protein delivery remains a major challenge owing to the multiple barriers in protein delivery process, such as protein encapsulation, endocytosis, endosomal escape and intracellular protein release. Recently, it was reported that fluorination on polymers is beneficial for their self-assembly and intracellular trafficking. We hypothesize the fluoropolymers can be used to encapsulate proteins and developed as a new class of carriers to break down the barriers during intracellular protein delivery. In this study, we successfully discovered an efficient and non-toxic polymer for protein delivery in a library of fluoropolymers. The lead material A6-2 in the library efficiently transported various proteins including bovine serum albumin, β-galactosidase, saporin and a cyclic hendecapeptide into the cytosol of living cells with minimal cytotoxicity. More importantly, activities of delivered proteins and peptides were maintained after delivery. The A6-2/saporin complex was further coated with a hyaluronic acid shell, and the yielding nanoparticle efficiently suppressed tumor growth in a breast cancer model by targeted protein delivery. This study provides a new insight into the design of efficient and biocompatible polymers for protein delivery. Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]