A Metallic Ion-Induced Self-Assembly Enabling Nanowire-Based Aerogels.

The controlled assembly of nanowires is one of the key challenges in the development of a range of functional 3D aerogels with unique physicochemical properties for practical applications. However, the deep understanding of the dynamic assemble process for fabricating nanowire aerogels remains elusive. Herein, a facile strategy is presented for the metallic ion-induced assembly of nanowires into macroscopic aerogels via a solution-based process. This method enables the interconnecting between polymer-decorated nanowires via metallic coordination, resulting in plenty of nanowire bundles with the same orientation. Besides, the coordinated binding strength of nanowires with different metallic ions is also discussed. The assembly mechanism that the metallic ions induced dynamic behavior of nanowires is revealed via molecular dynamics theoretical evaluation. These findings benefit for constructing nanowire-based aerogels with unique structural features and multi-function, which pave new opportunities for other material systems.

Dual-Functional Liposomes with Carbonic Anhydrase IX Antibody and BR2 Peptide Modification Effectively Improve Intracellular Delivery of Cantharidin to Treat Orthotopic Hepatocellular Carcinoma Mice.

Liposomal nanotechnology has a great potential to overcome the current major problems of chemotherapy. However, the lack of penetrability and targetability retards the successful delivery of liposomal carriers. Previously, we showed that BR2 peptide modification endowed cantharidin-loaded liposomes with intracellular penetration that enhanced the drug cytotoxic effects. Here, we aimed to improve the targeting delivery of drugs into cancer cells via highly expressed carbonic anhydrase IX (CA IX) receptors by modifying our previous catharidin-loaded BR2-liposomes with anti-CA IX antibody. A higher cellular uptake of dual-functional liposomes (DF-Lp) than other treatments was observed. Induction of CA IX over-expressing resulted in a higher cellular binding of DF-Lp; subsequently, blocking with excess antibodies resulted in a decreased cancer-cell association, indicating a specific targeting property of our liposomes towards CA IX expressed cells. After 3h tracking, most of the liposomes were located around the nucleus which confirmed the involvement of targeting intracellular delivery. Cantharidin loaded DF-Lp exhibited enhanced cytotoxicity in vitro and was most effective in controlling tumor growth in vivo in an orthotopic hepatocellular carcinoma model compared to other groups. Collectively, our results presented the advantage of the BR2 peptide and CA IX antibody combination to elevate the therapeutic potential of cantharidin loaded DF-liposomes.

The potential of liposomes with carbonic anhydrase IX to deliver anticancer ingredients to cancer cells in vivo.

Drug delivery nanocarriers, especially targeted drug delivery by liposomes are emerging as a class of therapeutics for cancer. Early research results suggest that liposomal therapeutics enhanced efficacy, while simultaneously reducing side effects, owing to properties such as more targeted localization in tumors and active cellular uptake. Here, we highlight the features of immunoliposomes that distinguish them from previous anticancer therapies, and describe how these features provide the potential for therapeutic effects that are not achievable with other modalities. While a large number of studies has been published, the emphasis here is placed on the carbonic anhydrase IX (CA-IX) and the conjugated liposomes that are likely to open a new chapter on drug delivery system by using immunoliposomes to deliver anticancer ingredients to cancer cells in vivo.

Dual-ligand modified liposomes provide effective local targeted delivery of lung-cancer drug by antibody and tumor lineage-homing cell-penetrating peptide.

The abilities of a drug delivery system to target and penetrate tumor masses are key factors in determining the system's chemotherapeutic efficacy. Here, we explored the utility of an anti-carbonic anhydrase IX (anti-CA IX) antibody and CPP33 dual-ligand modified triptolide-loaded liposomes (dl-TPL-lip) to simultaneously enhance the tumor-specific targeting and increase tumor cell penetration of TPL. In vitro, the dl-TPL-lip increased the cytotoxicity of TPL in CA IX-positive lung cancer cells, which showed tunable size (137.6 ± 0.8 nm), high-encapsulation efficiency (86.3 ± 2.6%) and sustained release. Dl-TPL-lip significantly improved the ability of liposomes to penetrate 3 D tumor spheroids and exhibited a superior inhibiting effect. Furthermore, pharmacokinetic studies in rats that received TPL liposomal formulations by endotracheal administration showed a reduced concentration of TPL (17.3%-30.6% compared to free TPL) in systemic circulation. After pulmonary administration in orthotopic lung tumor-bearing mice, dl-TPL-lip significantly enhanced TPL anti-cancer efficacy without apparent systemic toxicity. This dual-ligand modified liposomal vehicle presents a potential system for localized and targeted delivery of anti-cancer drugs to improve their efficacy.

Liposomes equipped with cell penetrating peptide BR2 enhances chemotherapeutic effects of cantharidin against hepatocellular carcinoma.

A main hurdle for the success of tumor-specific liposomes is their inability to penetrate tumors efficiently. In this study, we incorporated a cell-penetrating peptide BR2 onto the surface of a liposome loaded with the anticancer drug cantharidin (CTD) to create a system targeting hepatocellular carcinoma (HCC) cells more efficiently and effectively. The in vitro cytotoxicity assay comparing the loaded liposomes' effects on hepatocellular cancer HepG2 and the control Miha cells showed that CTD-loaded liposomes had a stronger anticancer effect after BR2 modification. The cellular uptake results of HepG2 and Miha cells further confirmed the superior ability of BR2-modified liposomes to penetrate cancer cells. The colocalization study revealed that BR2-modified liposomes could enter tumor cells and subsequently release drugs. A higher efficiency of delivery by BR2 liposomes as compared to unmodified liposomes was evident by evaluation of the HepG2 tumor spheroids penetration and inhibition. The biodistribution studies and anticancer efficacy results in vivo showed the significant accumulation of BR2-modified liposomes into tumor sites and an enhanced tumor inhibition. In conclusion, BR2-modified liposomes improve the anticancer potency of drugs for HCC.

Pulmonary delivery of triptolide-loaded liposomes decorated with anti-carbonic anhydrase IX antibody for lung cancer therapy.

Antibody-decorated liposomes can facilitate the precise delivery of chemotherapeutic drugs to the lung by targeting a recognition factor present on the surface of lung tumor cells. Carbonic anhydrase IX (CA IX) is an enzyme expressed on the surface of lung cancer cells with a restricted expression in normal lungs. Here, we explored the utility of anti-carbonic anhydrase IX (CA IX) antibody, conjugated to the surface of triptolide (TPL)-loaded liposomes (CA IX-TPL-Lips), to promote the therapeutic effects for lung cancer via pulmonary administration. It was found that the CA IX-TPL-Lips significantly improved the cellular uptake efficiency in both CA IX-positive human non-small cell lung cancer cells (A549) and A549 tumor spheroids, resulting in the efficient cell killing compared with free TPL and non-targeted TPL-Lips. In vivo, CA IX-Lips via pulmonary delivery showed specificity and a sustained release property resided up to 96 h in the lung, both of which improved the efficiency of TPL formulations in restraining tumor growth and significantly prolonged the lifespan of mice with orthotopic lung tumors. The results suggest that CA IX-decorated liposomes can potentially be used as an effective therapeutic strategy for lung cancer.

[An investigation of restoration of alveolar cleft with engineered bone].

OBJECTIVE: To investigate restoration of alveolar cleft with engineered bone constructed by sponge collagen protein combined bone mesenchymal stem cells (BMSC). METHODS: Twelve dogs were divided into 4 groups, the third incisor and alveolar bone with periosteum in bilateral maxilla were removed to form alveolar cleft model. The BMSCs were isolated from dog bone marrow. After being cultured and induced, the BMSCs were seeded in sponge collagen protein and cultured for 48 hours. The composites of BMSCs and collagen were implanted into the defect of alveolar cleft. After 12 weeks' feeding, those dogs were sacrificed. Three-dimensional CT and histological examination were used to observe the progress of bone formation. RESULTS: The defects healed at 12 weeks after being implant BMSCs-collagen composites, the width of engineered bone is resembled with positive control, but the height is less than positive control. CONCLUSIONS: The engineered bone can restore the defect of alveolar bone effectively, it can be used clinically to treat alveolar cleft.