Prevention of post-surgical abdominal adhesions by a novel biodegradable thermosensitive PECE hydrogel.

<p>Abstract</p> <p>Background</p> <p>Post-operative peritoneal adhesions are common and serious complications for modern medicine. We aim to prevent post-surgical adhesions using biodegradable and thermosensitive poly(ethylene glycol)-poly(ε-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) hydrogel. In this work, we investigated the effect of PECE hydrogel on preventing post-surgical abdominal adhesions in mouse and rat models.</p> <p>Results</p> <p>The PECE hydrogel in sol state could be transformed into gel in less than 20 s at 37°C. In addition, the PECE hydrogel could be easily adhered to the damaged peritoneal surfaces, and be gradually degraded and absorbed by the body within 14 days along with the healing of peritoneal wounds. A notable efficacy of the PECE hydrogel in preventing peritoneal adhesions was demonstrated in the animal models. In contrast, all untreated animals developed adhesions requiring sharp dissection. Furthermore, no significant histopathological changes were observed in main organs of the hydrogel-treated animals.</p> <p>Conclusion</p> <p>Our results suggested that the thermosensitive PECE hydrogel was an effective, safe, and convenient agent on preventing post-surgical intro-abdominal adhesions.</p

A novel Poly(ε-caprolactone)-Pluronic-Poly(ε-caprolactone) grafted Polyethyleneimine(PCFC-g-PEI), Part 1, synthesis, cytotoxicity, and in vitro transfection study

<p>Abstract</p> <p>Background</p> <p>Polyethyleneimine (PEI), a cationic polymer, is one of the successful and widely used vectors for non-viral gene transfection <it>in vitro</it>. However, its <it>in vivo </it>application was greatly limited due to its high cytotoxicity and short duration of gene expression. To improve its biocompatibility and transfection efficiency, PEI has been modified with PEG, folic acid, and chloroquine in order to improve biocompatibility and enhance targeting.</p> <p>Results</p> <p>Poly(ε-caprolactone)-Pluronic-Poly(ε-caprolactone) (PCFC) was synthesized by ring-opening polymerization, and PCFC-<it>g</it>-PEI was obtained by Michael addition reaction with GMA-PCFC-GMA and polyethyleneimine (PEI, 25 kD). The prepared PCFC-<it>g</it>-PEI was characterized by ¹H-NMR, SEC-MALLS. Meanwhile, DNA condensation, DNase I protection, the particle size and zeta potential of PCFC-<it>g</it>-PEI/DNA complexes were also determined. According to the results of flow cytometry and MTT assay, the synthesized PCFC-<it>g</it>-PEI, with considerable transfection efficiency, had obviously lower cytotoxicity against 293 T and A549 cell lines compared with that of PEI 25 kD.</p> <p>Conclusion</p> <p>The cytotoxicity and <it>in vitro </it>transfection study indicated that PCFC-<it>g</it>-PEI copolymer prepared in this paper was a novel gene delivery system with lower cytotoxicity and considerable transfection efficiency compared with commercial PEI (25 kD).</p

Biodegradable Thermosensitive Hydrogel for SAHA and DDP Delivery: Therapeutic Effects on Oral Squamous Cell Carcinoma Xenografts

Background: OSCC is one of the most common malignancies and numerous clinical agents currently applied in combinative chemotherapy. Here we reported a novel therapeutic strategy, SAHA and DDP-loaded PECE (SAHA-DDP/PECE), can improve the therapeutic effects of intratumorally chemotherapy on OSCC cell xenografts. Objective/Purpose: The objective of this study was to evaluate the therapeutic efficacy of the SAHA-DDP/PECE in situ controlled drug delivery system on OSCC cell xenografts. Methods: A biodegradable and thermosensitive hydrogel was successfully developed to load SAHA and DDP. Tumorbeared mice were intratumorally administered with SAHA-DDP/PECE at 50 mg/kg (SAHA) +2 mg/kg (DDP) in 100 ul PECE hydrogel every two weeks, SAHA-DDP at 50 mg/kg(SAHA) +2 mg/kg(DDP) in NS, 2 mg/kg DDP solution, 50 mg/kg SAHA solution, equal volume of PECE hydrogel, or equal volume of NS on the same schedule, respectively. The antineoplastic actions of SAHA and DDP alone and in combination were evaluated using the determination of tumor volume, immunohistochemistry, western blot, and TUNEL analysis. Results: The hydrogel system was a free-flowing sol at 10uC, become gel at body temperature, and could sustain more than 14 days in situ. SAHA-DDP/PECE was subsequently injected into tumor OSCC tumor-beared mice. The results demonstrated that such a strategy as this allows the carrier system to show a sustained release of SAHA and DDP in vivo, and coul

5-FU-hydrogel inhibits colorectal peritoneal carcinomatosis and tumor growth in mice

<p>Abstract</p> <p>Background</p> <p>Colorectal peritoneal carcinomatosis (CRPC) is a common form of systemic metastasis of intra-abdominal cancers. Intraperitoneal chemotherapy is a preferable option for colorectal cancer. Here we reported that a new system, 5-FU-loaded hydrogel system, can improve the therapeutic effects of intraperitoneal chemotherapy.</p> <p>Methods</p> <p>A biodegradable PEG-PCL-PEG (PECE) triblock copolymer was successfully synthesized. The biodegradable and temperature sensitive hydrogel was developed to load 5-FU. Methylene blue-loaded hydrogel were also developed for visible observation of the drug release. The effects and toxicity of the 5-FU-hydrogel system were evaluated in a murine CRPC model.</p> <p>Results</p> <p>The hydrogel system is an injectable flowing solution at ambient temperature and forms a non-flowing gel depot at physiological temperature. 5-FU-hydrogel was subsequently injected into abdominal cavity in mice with CT26 cancer cells peritoneal dissemination. The results showed that the hydrogel delivery system prolonged the release of methylene blue; the 5-FU-hydrogel significantly inhibited the peritoneal dissemination and growth of CT26 cells. Furthermore, intraperitoneal administration of the 5-FU-hydrogel was well tolerated and showed less hematologic toxicity.</p> <p>Conclusions</p> <p>Our data indicate that the 5-FU-hydrogel system can be considered as a new strategy for peritoneal carcinomatosis, and the hydrogel may provide a potential delivery system to load different chemotherapeutic drugs for peritoneal carcinomatosis of cancers.</p

TRAIL and curcumin codelivery nanoparticles enhance TRAIL-induced apoptosis through upregulation of death receptors

Active targeting nanoparticles were developed to simultaneously codeliver tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and Curcumin (Cur). In the nanoparticles (TRAIL-Cur-NPs), TRAIL was used as both active targeting ligand and therapeutic agent, and Cur could upregulate death receptors (DR4 and DR5) to increase the apoptosis-inducing effects of TRAIL. Compared with corresponding free drugs, TRAIL-Cur-NPs group showed enhanced cellular uptake, cytotoxicity and apoptosis induction effect on HCT116 colon cancer cells. In addition, in vivo anticancer studies suggested that TRAIL-Cur-NPs had superior therapeutic effect on tumors without obvious toxicity, which was mainly due to the high tumor targeting and synergistic effect of TRAIL and Cur. The synergistic mechanism of improved antitumor efficacy was proved to be upregulation of DR4 and DR5 in tumor cells induced by Cur. Thus, the prepared codelivery nanoparticles may have potential applications in colorectal cancer therapy

Engineered fluorescent carbon dots as promising immune adjuvants to efficiently enhance cancer immunotherapy

Engineered fluorescent carbon dots as promising immune adjuvants to efficiently enhance cancer immunotherap

A multifunctional ‘golden cicada’ nanoplatform breaks the thermoresistance barrier to launch cascade augmented synergistic effects of photothermal/gene therapy

Abstract Background Photothermal therapy (PTT) is taken as a promising strategy for cancer therapy, however, its applicability is hampered by cellular thermoresistance of heat shock response and insufficient accumulation of photothermal transduction agents in the tumor region. In consideration of those limitations, a multifunctional “Golden Cicada” nanoplatform (MGCN) with efficient gene delivery ability and excellent photothermal effects is constructed, overcoming the thermoresistance of tumor cells and improving the accumulation of indocyanine green (ICG). Results Down-regulation of heat shock protein 70 (HSP70) makes tumor cells more susceptible to PTT, and a better therapeutic effect is achieved through such cascade augmented synergistic effects. MGCN has attractive features with prolonged circulation in blood, dual-targeting capability of CD44 and sialic acid (SA) receptors, and agile responsiveness of enzyme achieving size and charge double-variable transformation. It proves that, on the one hand, MGCN performs excellent capability for HSP70-shRNA delivery, resulting in breaking the cellular thermoresistance mechanism, on the other hand, ICG enriches in tumor site specifically and possesses a great thermal property to promoted PTT. Conclusions In short, MGCN breaks the protective mechanism of cellular heat stress response by downregulating the expression of HSP70 proteins and significantly augments synergistic effects of photothermal/gene therapy via cascade augmented synergistic effects