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Membrane encapsulated nanoparticles and method of use

A nanoparticle and plasma membrane technology, applied in chemical instruments and methods, medical preparations containing active ingredients, pharmaceutical formulations, etc., can solve problems such as difficulties in nanoparticle functionalization, inability to replicate complex protein composition, and protein denaturation.

Active Publication Date: 2014-06-11
RGT UNIV OF CALIFORNIA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] Although great efforts have been made to bridge the gap between synthetic nanomaterials and biological entities, RBC-mimicking delivery vehicles remain elusive for biomedical researchers
A major challenge lies in the difficulty of functionalizing nanoparticles through the complex surface chemistry of biological cells
Despite recent advances in reducing macrophage phagocytosis of polystyrene beads following binding to the immunosuppressive RBC membrane protein (CD47) (11), current chemical-based bioconjugation techniques frequently result in protein denaturation
Additionally, these bottom-up approaches are largely incapable of replicating complex protein compositions on nanoscale substrates

Method used

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Examples

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Effect test

Embodiment 1

[0141] Erythrocyte membrane-camouflaged polymer nanoparticles as a biomimetic delivery platform

[0142] By extruding poly(lactic-co-glycolic acid) (PLGA) particles with preformed RBC membrane-derived vesicles, the inventors coated sub-100 nm polymers with bilayer RBC membranes comprising lipids and corresponding surface proteins particles. This approach aims to camouflage the nanoparticle surface with the erythrocyte exterior for long circulation while retaining the suitability of the polymer core. The inventors report the physical characteristics, physicochemical properties, protein content, pharmacokinetics, and biodistribution of this bioinspired nanoparticle delivery platform.

[0143] The preparation process of RBC membrane-coated nanoparticles is divided into two parts: obtaining membrane vesicles from RBCs and vesicle-particle fusion ( figure 1 ). The derivation of RBC membrane vesicles followed a previously reported method with minor modifications (13). Briefly, R...

Embodiment 2

[0212] Erythrocyte membrane-cloaked polymer nanoparticles for controlled drug loading and release

[0213] Polymeric nanoparticles (NPs) cloaked by red blood cell membranes (RBCm) confer the combined advantages of long circulation life and controlled drug retention and release. In this paper, for the development of this cell-mimicking NP platform for advanced drug delivery applications, the inventors conducted studies to gain a better understanding of its drug loading, drug release kinetics, and cell-based efficacy. Specifically, to study drug release from RBCm-cloaked NPs, the inventors compared two strategies for loading doxorubicin (DOX), a model anticancer drug, into RBCm-cloaked NPs: physical encapsulation and chemical couple couplet. In vitro efficacy was tested by using the acute myeloid leukemia (AML) Kasumi-1 cell line.

[0214]The inventors found that the chemical conjugation strategy resulted in a more sustained drug release profile. Furthermore, by formulating P...

Embodiment 3

[0303] Nanoparticles with cancer cell membranes for personalized immunotherapy

[0304] This example provides an immunotherapeutic system that has several advantages over existing methods.

[0305] 1) Current strategies focus only on individual tumor-associated antigens (TAAs) expressed by the general cancer type in question. Cancer is a heterogeneous disease, and one limitation of such an approach is that the antigen expression of one patient's cancer can be quite different from another patient's. This results in a less than optimal percentage of patients being actual candidates for such treatment. Another problem is that targeting a single TAA results in a weaker overall immune response against the cancer, allowing it to eventually mutate and develop resistance. The described invention addresses these issues by tailoring treatment to each individual patient by collecting membrane material from autologous tumors. This approach allows for the precise re-creation of antigen ...

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Abstract

Provided are nanoparticles, method of using and making thereof. The invention nanoparticle comprises a) an inner core comprising a non-cellular material; and b) an outer surface comprising a cellular membrane derived from a cell or a membrane derived from a virus. Medicament delivery systems or pharmaceutical compositions comprising the inventive nanoparticles are also provided. The present invention further provides immunogenic compositions comprising the inventive nanoparticles, and methods of use the inventive immunogenic compositions for eliciting an immune response and for treating or preventing disease or condition, such as neoplasm or cancer, or disease or conditions associated with cell membrane inserting toxin. Vaccines comprising the immunogenic composition comprising the nanoparticles of the present invention are also provided.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to US Provisional Application Serial No. 61 / 492,626, filed June 2, 2011, which is hereby incorporated by reference in its entirety. [0003] Statement Regarding Federally Sponsored Research [0004] This invention was made with Government support under NSF Grant No. CMMI1031239, NIH Grant No. U54CA119335, and DMR Grant No. 1216461. The government has certain rights in this invention. field of invention [0005] The present invention relates to methods and compositions for the delivery of synthetic nanoparticulate materials, including pharmaceutically active agents, encapsulated by cell membranes. Background of the invention [0006] Long-circulating polymeric nanoparticles have significant clinical utility as they promise sustained systemic delivery and better targeting through passive and active mechanisms (1-3). Different approaches including modification of particle size, surface,...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/51
CPCA61K39/0011A61K39/39A61K9/148C07K14/005A61K45/06A61K2039/55555A61K9/51A61K39/085A61K9/5031A61K9/5068A61K9/5146A61K9/5176A61K39/001102A61K2039/80A61P31/04A61P31/10A61P35/00A61P37/04
Inventor 张良方罗尼·弘博·方哲铭(杰克)·胡乔纳森·科普
Owner RGT UNIV OF CALIFORNIA
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