Fully synthetic polymer vesicles for intracellular delivery of antibodies in live cells

Cantón, Irene; Massignani, Marzia; Patikarnmonthon, Nisa; Chierico, Luca; Robertson, J. David; Renshaw, Stephen A.; Warren, Nicholas J.; Madsen, Jeppe P.; Armes, Steven P.; Lewis, Andrew L.; Battaglia, Giuseppe

doi:10.1096/fj.12-212183

Cited by 66 publications

(67 citation statements)

References 40 publications

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“…This approach has enabled the delivery of many types of cargos including plasmid DNA, small molecules, antibodies, and small nanoparticles (Lomas et al 2007(Lomas et al , 2008Massignani et al 2010;Canton et al 2013). …”

Section: Exploiting Endocytosis For Nanomedicinesmentioning

confidence: 99%

Exploiting Endocytosis for Nanomedicines

Akinc

Battaglia

2013

Cold Spring Harbor Perspectives in Biology

189

169

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In this article, we briefly review the endocytic pathways used by cells, pointing out their defining characteristics and highlighting physical limitations that may direct the internalization of nanoparticles to a subset of these pathways. A more detailed description of these pathways is presented in the literature. We then focus on the endocytosis of nanomedicines and present how various nanomaterial parameters impact these endocytic processes. This topic is an area of active research, motivated by the recognition that an improved understanding of how nanomaterials interact at the molecular, cellular, and whole-organism level will lead to the design of better nanomedicines in the future. Next, we briefly review some of the important nanomedicines already on the market or in clinical development that serve to exemplify how endocytosis can be exploited for medical benefit. Finally, we present some key unanswered questions and remaining challenges to be addressed by the field.

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Section: Exploiting Endocytosis For Nanomedicinesmentioning

confidence: 99%

Exploiting Endocytosis for Nanomedicines

Akinc

Battaglia

2013

Cold Spring Harbor Perspectives in Biology

189

169

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“…These polymersomes are formed through the self-assembly of amphiphilic copolymers in aqueous media, 7 and combine the advantages of long-term stability with the potential to encapsulate a broad range of cargoes. [8][9][10] We have previously demonstrated that the pH sensitive block copolymer poly(2-(methacryloyloxy) ethyl-phosphorylcholine)-co-poly(2-(diisopropylamino)ethyl methacrylate) (PMPC-PDPA) can combine specific cellular targeting efficiency (through the PMPC block and its affinity toward the scavenger receptor B1), 11 with effective endosomal escape and cytosolic delivery following internalisation (by the pH sensitive PDPA). 8,12 In this study, we describe the half life and bio-distribution of the PMPC-PDPA polymersomes in vivo, showing the dynamics of accumulation within different tissues.…”

Section: Introductionmentioning

confidence: 99%

Targeting mononuclear phagocytes for eradicating intracellular parasites

Rizzello

Robertson

Elks

et al. 2017

Preprint

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Mononuclear phagocytes such as monocytes, tissue-specific macrophages and dendritic cells are primary actors in both innate and adaptive immunity, as well as tissue homoeostasis. They have key roles in a range of physiological and pathological processes, so any strategy targeting these cells will have wide-ranging impact. These phagocytes can be parasitized by intracellular bacteria, turning them from housekeepers to hiding places and favouring chronic and/or disseminated infection. One of the most infamous is the bacteria that cause tuberculosis, which is the most pandemic and one of the deadliest disease with one third of the world's population infected, and 1.8 million deaths worldwide in 2015. Here we demonstrate the effective targeting and intracellular delivery of antibiotics to both circulating monocytes and resident macrophages, using pH sensitive nanoscopic polymersomes made of poly(2-(methacryloyloxy)ethyl phosphorylcholine)-co-poly(2-(diisopropylamino)ethyl methacrylate) (PMPC-PDPA). Polymersome selectivity to mononuclear phagocytes is demonstrated and ascribed to the polymerised phosphorylcholine motifs affinity toward scavenger receptors. Finally, we demonstrate the successful exploitation of this targeting for the effective eradication of intracellular bacteria that cause tuberculosis Mycobacterium tuberculosis as well as other intracellular parasites including the Mycobacterium bovis, Mycobacterium marinum and the most common bacteria associated with antibiotic resistance, the Staphylococcus aureus.

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“…PDPA-based polymersomes have been used for intracellular delivery of DNA (14), antibodies (15), antibiotics (28), anticancer drugs (12,13), and peptides (29). Particularly, for cancer cells, an efficient cytoplasmic delivery improves the drug efficacy (12).…”

Section: Introductionmentioning

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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Fully synthetic polymer vesicles for intracellular delivery of antibodies in live cells

Cited by 66 publications

References 40 publications

Exploiting Endocytosis for Nanomedicines

Exploiting Endocytosis for Nanomedicines

Targeting mononuclear phagocytes for eradicating intracellular parasites

Paclitaxel-Loaded Polymersomes for Enhanced Intraperitoneal Chemotherapy

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