Self-Assembled Lipid−Polymer Hybrid Nanoparticles: A Robust Drug Delivery Platform

Zhang, Liangfang; Chan, Juliana M.; Gu, Frank; Rhee, June; Wang, Andrew Z.; Radovic‐Moreno, Aleksandar F.; Alexis, Frank; Langer, Robert; Farokhzad, Omid C.

doi:10.1021/nn800275r

Cited by 865 publications

(826 citation statements)

References 18 publications

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“…Briefly, to prepare the PLGA NPs, PLGA (4 mg/mL) in acetonitrile (ACN) was added dropwise into 3 mL of endotoxin free water and stirred at room temperature under a vacuum until the ACN completely evaporated (approximately 3 hours). To prepare the DOTAP core-shell NPs 32 , PLGA (4 mg/mL) in ACN was added dropwise into 3 mL of 4% ethanol solution containing lecithin/DOTAP (7:3 molar ratio) with a weight ratio of 15% to the PLGA polymer solution pre-heated to 55.0 °C. This solution was vortexed for 3 min and stirred at room temperature under a vacuum until the ACN completely evaporated.…”

Section: Methodsmentioning

confidence: 99%

Antigen-capturing nanoparticles improve the abscopal effect and cancer immunotherapy

et al. 2017

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Immunotherapy holds tremendous promise for improving cancer treatment1. Administering radiotherapy with immunotherapy has been shown to improve immune responses and can elicit an “abscopal effect”2. Unfortunately, response rates for this strategy remain low3. Herein, we report an improved cancer immunotherapy approach that utilizes antigen-capturing nanoparticles (AC-NPs). We engineered several AC-NPs formulations and demonstrated that the set of protein antigens captured by each AC-NP formulation is dependent upon NP surface properties. We showed that AC-NPs deliver tumor specific proteins to antigen-presenting cells and significantly improve the efficacy of αPD-1 treatment using the B16F10 melanoma model, generating up to 20% cure rate as compared to 0% without AC-NPs. Mechanistic studies revealed that AC-NPs induced an expansion of CD8+ cytotoxic T cells and increased both CD4+/Treg and CD8+/Treg ratios. Our work presents a novel strategy for improving cancer immunotherapy with nanotechnology.

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Section: Methodsmentioning

confidence: 99%

Antigen-capturing nanoparticles improve the abscopal effect and cancer immunotherapy

et al. 2017

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“…43 Therefore, the serum-conditioned experiment has been currently serving as a fundamental model for the predictive evaluation on the in vivo stability of most nanocarriers. 44 In our study, the preliminary serum-tolerance assess was also conducted in 10% serum solution, which is a typical serum concentration in most in vitro cell culture studies. 45 Similar to the serum-free case, a significant amount of sediments appeared just after 5 h standing in lGO and lGO/mPEG dispersions, whereas nearly no sediments were detected over the 8-day observation for the lGO/NP (1:10) dispersion ( Figure 1C).…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Graphene-Based Anticancer Nanosystem and Its Biosafety Evaluation Using a Zebrafish Model

et al. 2013

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In this paper, a facile strategy to develop graphenebased delivery nanosystems for effective drug loading and sustained drug release was proposed and validated. Specifically, biocompatible naphthalene-terminated PEG (NP) and anticancer drugs (curcumin or doxorubicin (DOX)) were simultaneously integrated onto oxidized graphene (GO), leading to selfassembled, nanosized complexes. It was found that the oxidation degree of GO had a significant impact on the drug-loading efficiency and the structural stability of nanosystems. Interestingly, the nanoassemblies resulted in more effective cellular entry of DOX in comparison with free DOX or DOX-loaded PEGpolyester micelles at equivalent DOX dose, as demonstrated by confocal microscopy studies. Moreover, the nanoassemblies not only exhibited a sustained drug release pattern without an initial burst release, but also significantly improved the stability of formulations which were resistant to drug leaking even in the presence of strong surfactants such as aromatic sodium benzenesulfonate (SBen) and aliphatic sodium dodecylsulfonate (SDS). In addition, the nanoassemblies without DOX loading showed negligible in vitro cytotoxicity, whereas DOX-loaded counterparts led to considerable toxicity against HeLa cells. The DOX-mediated cytotoxicity of the graphene-based formulation was around 20 folds lower than that of free DOX, most likely due to the slow DOX release from complexes. A zebrafish model was established to assess the in vivo safety profile of curcumin-loaded nanosystems. The results showed they were able to excrete from the zebrafish body rapidly and had nearly no influence on the zebrafish upgrowth. Those encouraging results may prompt the advance of graphene-based nanotherapeutics for biomedical applications.

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“…Self‐assembled lipid‐polymer hybrid nanoparticles have been demonstrated to be a robust drug delivery platform 248, 249, 250. These nanoparticles comprise a hydrophobic PLGA core, a hydrophilic PEG shell, and a lipid (lecithin) monolayer at the interface of the core and shell that acts as a molecular fence to enhance drug retention 248.…”

Section: Nanoparticle‐mediated Cptmentioning

confidence: 99%

Chemophototherapy: An Emerging Treatment Option for Solid Tumors

et al. 2016

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Near infrared (NIR) light penetrates human tissues with limited depth, thereby providing a method to safely deliver non‐ionizing radiation to well‐defined target tissue volumes. Light‐based therapies including photodynamic therapy (PDT) and laser‐induced thermal therapy have been validated clinically for curative and palliative treatment of solid tumors. However, these monotherapies can suffer from incomplete tumor killing and have not displaced existing ablative modalities. The combination of phototherapy and chemotherapy (chemophototherapy, CPT), when carefully planned, has been shown to be an effective tumor treatment option preclinically and clinically. Chemotherapy can enhance the efficacy of PDT by targeting surviving cancer cells or by inhibiting regrowth of damaged tumor blood vessels. Alternatively, PDT‐mediated vascular permeabilization has been shown to enhance the deposition of nanoparticulate drugs into tumors for enhanced accumulation and efficacy. Integrated nanoparticles have been reported that combine photosensitizers and drugs into a single agent. More recently, light‐activated nanoparticles have been developed that release their payload in response to light irradiation to achieve improved drug bioavailability with superior efficacy. CPT can potently eradicate tumors with precise spatial control, and further clinical testing is warranted.

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Self-Assembled Lipid−Polymer Hybrid Nanoparticles: A Robust Drug Delivery Platform

Cited by 865 publications

References 18 publications

Antigen-capturing nanoparticles improve the abscopal effect and cancer immunotherapy

Antigen-capturing nanoparticles improve the abscopal effect and cancer immunotherapy

Graphene-Based Anticancer Nanosystem and Its Biosafety Evaluation Using a Zebrafish Model

Chemophototherapy: An Emerging Treatment Option for Solid Tumors

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