A Comparison of Intravenous plus Intraperitoneal Chemotherapy with Intravenous Chemotherapy Alone for the Treatment of Gastric Cancer: A Meta-Analysis

Yang, Sheng; Feng, Rui; Pan, Zhizhong Z.; Jiang, Tao; Xu, Qian; Chen, Qiang

doi:10.1038/srep12538

Cited by 18 publications

(12 citation statements)

References 23 publications

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“…Such dual pathway allows payload delivery to both small avascular nodules and to large vascular tumors. This is an important advantage, as a number of clinical studies on PC indicate that combining systemic and IP chemotherapy results in better outcome than either route alone [58]. …”

Section: Discussionmentioning

confidence: 99%

iRGD peptide conjugation potentiates intraperitoneal tumor delivery of paclitaxel with polymersomes

et al. 2016

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Polymersomes are versatile nanoscale vesicles that can be used for cytoplasmic delivery of payloads. Recently, we demonstrated that pH-sensitive polymersomes exhibit an intrinsic selectivity towards intraperitoneal tumor lesions. A tumor homing peptide, iRGD, harbors a cryptic C-end Rule (CendR) motif that is responsible for neuropilin-1 (NRP-1) binding and for triggering extravasation and tumor penetration of the peptide. iRGD functionalization increases tumor selectivity and therapeutic efficacy of systemic drug-loaded nanoparticles in many tumor models. Here we studied whether intraperitoneally administered paclitaxel-loaded iRGD-polymersomes show improved efficacy in the treatment of peritoneal carcinomatosis. First, we demonstrated that the pH-sensitive polymersomes functionalized with RPARPAR (a prototypic CendR peptide) or iRGD internalize in the cells that express NRP-1, and that internalized polymersomes release their cargo inside the cytosol. CendR-targeted polymersomes loaded with paclitaxel were more cytotoxic on NRP-1-positive cells than on NRP-1-negative cells. In mice bearing peritoneal tumors of gastric (MKN-45P) or colon (CT26) origin, intraperitoneally administered RPARPAR and iRGD-polymersomes showed higher tumor-selective accumulation and penetration than untargeted polymersomes. Finally, iRGD-polymersomes loaded with paclitaxel showed improved efficacy in peritoneal tumor growth inhibition and in suppression of local dissemination compared to the pristine paclitaxel-polymersomes or Abraxane. Our study demonstrates that iRGD-functionalization improves efficacy of paclitaxel-polymersomes for intraperitoneal treatment of peritoneal carcinomatosis.

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Section: Discussionmentioning

confidence: 99%

iRGD peptide conjugation potentiates intraperitoneal tumor delivery of paclitaxel with polymersomes

et al. 2016

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“…After injection into the peritoneal cavity, a drug or a nanocarrier, is taken up by the surrounding peritoneal tissues, and from there spread into other body compartments via the circulation [66] . Using the IP route not only avoids systemic distribution of the drug, but also provides high concentrations, locally, which are then able to act on the peritoneal tissues directly [67] . Many studies have shown the use of the IP route for cancer therapy including chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

Engineering hepatitis B virus core particles for targeting HER2 receptors in vitro and in vivo

et al. 2017

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Hepatitis B Virus core (HBc) particles have been studied for their potential as drug delivery vehicles for cancer therapy. HBc particles are hollow nano-particles of 30–34 nm diameter and 7 nm thick envelopes, consisting of 180–240 units of 21 kDa core monomers. They have the capacity to assemble/dis-assemble in a controlled manner allowing encapsulation of various drugs and other biomolecules. Moreover, other functional motifs, i.e. receptors, receptor binding sequences, peptides and proteins can be expressed. This study focuses on the development of genetically modified HBc particles to specifically recognise and target human epidermal growth factor receptor-2 (HER2)-expressing cancer cells, in vitro and in vivo, for future cancer therapy. The non-specific binding capacity of wild type HBc particles was reduced by genetic deletion of the sequence encoding arginine-rich domains. A specific HER2-targeting was achieved by expressing the ZHER2 affibodies on the HBc particles surface. In vitro studies showed specific uptake of ZHER2-ΔHBc particles in HER2 expressing cancer cells. In vivo studies confirmed positive uptake of ZHER2-ΔHBc particles in HER2-expressing tumours, compared to non-targeted ΔHBc particles in intraperitoneal tumour-bearing mice models. The present results highlight the potential of these nanocarriers in targeting HER2-positive metastatic abdominal cancer following intra-peritoneal administration.

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“…Microscopic analysis of the distribution of polymersomes in peritoneal and subcutaneous tumors suggested that polymersomes target peritoneal tumors through a combination of direct local penetration and indirect circulation-mediated homing. Such dual targeting is important, as a number of clinical studies indicate that combination of IV and IP chemotherapy for peritoneal carcinomatosis results in better outcome (decreased rate of metastasis, and decreased peritoneal recurrence) than either therapy alone (37). Paclitaxel is very poorly absorbed into the systemic circulation when administered by the IP route, with peak levels in the peritoneal cavity of 1000-fold higher than in the plasma (38), necessitating supplementation of IP paclitaxel with systemic chemotherapies.…”

Section: Discussionmentioning

confidence: 99%

Paclitaxel-Loaded Polymersomes for Enhanced Intraperitoneal Chemotherapy

Simón‐Gracia

Hunt

Scodeller

et al. 2016

Molecular Cancer Therapeutics

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Peritoneal carcinomatosis is present in more than 60% of gastric cancer, 40% of ovarian cancer, and 35% of colon cancer patients. It is the second most common cause of cancer mortality, with a median survival of 1–3 months. Cytoreductive surgery combined with intraperitoneal chemotherapy is the current clinical treatment, but achieving curative drug accumulation and penetration in peritoneal carcinomatosis lesions remains an unresolved challenge. Here we employed flexible and pH-sensitive polymersomes for payload delivery to peritoneal gastric (MKN-45P) and colon (CT26) carcinoma in mice. Polymersomes were loaded with Paclitaxel® and in vitro drug release was studied as a function of pH and time. Paclitaxel-loaded polymersomes remained stable in aqueous solution at neutral pH for up to four months. In cell viability assay on cultured cancer cell lines (MKN-45P, SKOV3, CT26), Paclitaxel-loaded polymersomes were more toxic than free drug or albumin-bound Paclitaxel (Abraxane®). Intraperitoneally administered fluorescent polymersomes accumulated in malignant lesions, and immunofluorescence revealed intense signal inside tumors with no detectable signal in control organs. A dual targeting of tumors was observed: direct (circulation independent) penetration, and systemic, blood vessel-associated accumulation. Finally, we evaluated preclinical antitumor efficacy of polymersomes-paclitaxel in treatment of MKN-45P disseminated gastric carcinoma using a total dose of 7 mg/kg. Experimental therapy with polymersome-Paclitaxel improved the therapeutic index of drug over Paclitaxel-Cremophor and Abraxane®, as evaluated by intraperitoneal tumor burden and number of metastatic nodules. Our findings underline the potential utility of the polymersome platform for delivery of drugs and imaging agents to peritoneal carcinomatosis lesions.

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A Comparison of Intravenous plus Intraperitoneal Chemotherapy with Intravenous Chemotherapy Alone for the Treatment of Gastric Cancer: A Meta-Analysis

Cited by 18 publications

References 23 publications

iRGD peptide conjugation potentiates intraperitoneal tumor delivery of paclitaxel with polymersomes

iRGD peptide conjugation potentiates intraperitoneal tumor delivery of paclitaxel with polymersomes

Engineering hepatitis B virus core particles for targeting HER2 receptors in vitro and in vivo

Paclitaxel-Loaded Polymersomes for Enhanced Intraperitoneal Chemotherapy

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