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Polypeptide based drug carriers for ...

Aluri, Suhaas Rayudu.

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Polypeptide based drug carriers for anti cancer applications.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Polypeptide based drug carriers for anti cancer applications./
作者:	Aluri, Suhaas Rayudu.
面頁冊數:	170 p.
附註:	Source: Dissertation Abstracts International, Volume: 75-02(E), Section: B.
Contained By:	Dissertation Abstracts International75-02B(E).
標題:	Health Sciences, Pharmacy. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3598156
ISBN:	9781303466342

Polypeptide based drug carriers for anti cancer applications.
Aluri, Suhaas Rayudu.

Polypeptide based drug carriers for anti cancer applications. - 170 p.

Source: Dissertation Abstracts International, Volume: 75-02(E), Section: B.

Thesis (Ph.D.)--University of Southern California, 2013.

This item is not available from ProQuest Dissertations & Theses.

Chapter 1: The tumor microenvironment provides multiple cues that may be exploited to improve the efficacy of established chemotherapeutics; furthermore, polypeptides are uniquely situated to capitalize on these signals. Peptides provide: 1) a rich repertoire of biologically specific interactions to draw upon; 2) environmentally-responsive phase behaviors, which may be tuned to respond to signatures of disease; 3) opportunities to direct self-assembly; 4) control over routes of biodegradation; 5) the option to seamlessly combine functionalities into a single polymer via a one-step biosynthesis. As development of cancer-targeted nanocarriers expands, peptides provide a unique source of functional units that may target disease. This dissertation explores potential microenvironmental physiology indicative of tumors and peptides that have demonstrated an ability to target and deliver to these signals.

ISBN: 9781303466342Subjects--Topical Terms:

1017737
Health Sciences, Pharmacy.

Polypeptide based drug carriers for anti cancer applications.
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100 1 $a Aluri, Suhaas Rayudu. $3 3170780
245 1 0 $a Polypeptide based drug carriers for anti cancer applications.
300 $a 170 p.
500 $a Source: Dissertation Abstracts International, Volume: 75-02(E), Section: B.
500 $a Advisers: Andrew J. Mackay; Alan L. Epstein.
502 $a Thesis (Ph.D.)--University of Southern California, 2013.
506 $a This item is not available from ProQuest Dissertations & Theses.
506 $a This item must not be sold to any third party vendors.
520 $a Chapter 1: The tumor microenvironment provides multiple cues that may be exploited to improve the efficacy of established chemotherapeutics; furthermore, polypeptides are uniquely situated to capitalize on these signals. Peptides provide: 1) a rich repertoire of biologically specific interactions to draw upon; 2) environmentally-responsive phase behaviors, which may be tuned to respond to signatures of disease; 3) opportunities to direct self-assembly; 4) control over routes of biodegradation; 5) the option to seamlessly combine functionalities into a single polymer via a one-step biosynthesis. As development of cancer-targeted nanocarriers expands, peptides provide a unique source of functional units that may target disease. This dissertation explores potential microenvironmental physiology indicative of tumors and peptides that have demonstrated an ability to target and deliver to these signals.
520 $a Chapter 2: Peptide amphiphiles (PAs) self-assemble nanostructures with potential applications in drug delivery and tissue engineering. Some PAs share environmentally responsive behavior with their peptide components. Here we report a new type of PAs biologically inspired from human tropoelastin. Due to their biodegradability, biocompatibility, and environmental responsiveness, elastin-inspired biopolymers are an emerging platform for drug and cell delivery; furthermore, the discovery of ELPAs may provide a new and useful approach to engineer these materials into stimuli-responsive gels and drug carriers.
520 $a Chapter 3: B-cell lymphomas are widely occurring malignancies which have an incidence rate of 27 per 100,000 subjects per year. A vital component of therapy for B-cell lymphomas is a chimeric antibody, RituxanRTM (RTXN), which has appreciable clinical activity. RTXN targets B-cell surface receptor, CD20, and induces tumor regression by a variety of mechanisms. One of the mechanisms of action is through Fc crosslinking of RTXN by FcR; expressing effector cells (NK cells, Macrophages, etc). This phenomenon was confirmed in vitro by inducing hyper-crosslinking via 2° antibodies and chemical means. To enhance the apoptotic effects of RTXN in CD20+ B-cell lymphomas, we designed antibody core protein nanoworms (ACPPNs) which take advantage of this phenomenon. These novel ACPPNs are multimeric assemblies of anti-CD20 scFv-Elastin like polypeptides (ELPs) fusions. These mutimeric `nanoworms' are active and competitively bind CD20 on B-cell lymphoma cell lines (Burkitt's and Diffuse large B-cell lymphomas). These results demonstrate that novel recombinant ACPPNs are a first generation small molecule free therapeutic for the treatment of B-cell related malignancies and disorders.
520 $a Chapter 4: While some amphipathic peptides interact directly with membranes, many peptides have potentially useful environmentally-responsive behavior only aqueous solution. We developed a simple approach to modify water-soluble polypeptides via an amino terminal lysine using two palmitoyl lipids. As a model polypeptide, we used our approach to graft short elastin like polypeptide (ELPs) sequences to the surface of liposomes using Elastin like peptide amphiphiles (ELPAs). High molecular weight ELPs undergo an environmentally responsive phase transition above a solution critical temperature but the transition is not sufficient to cause membrane rupture. Utilizing surface grafted ELPs we can both stabilize and destabilize a lipid membrane in response to temperature. The incorporation of two proximal lipid groups yielded an excellent degree of stabilization to a lipid membrane. This low cost approach avoids chemistry using expensive or pH-labile lipids, is compatible with solid phase chemistry, and is not mediated by bulky peptide domains. Incorporation of this novel conjugate on a lipid membrane causes rapid leakage of content when heated to 45°C. Leakage of contents was confirmed to be due to membrane permeabilization. Surface polymer conformation determines the extent of content leakage where low grafting density or `mushroom' conformation yields higher leakage than polymers in `brush' conformation. Also liposomes formulated with a `brush' conformation remained stable at all temperatures and behaved similar to PEG grafted liposomes. The peptide conformation influences liposome uptake with the `mushroom' conformation allowing for high cell uptake compared to the `brush' conformation. Utilizing these liposomes, doxorubicin (DOX) was successfully encapsulated and delivered to cancer cells. (Abstract shortened by UMI.).
590 $a School code: 0208.
650 4 $a Health Sciences, Pharmacy. $3 1017737
650 4 $a Nanotechnology. $3 526235
650 4 $a Engineering, Materials Science. $3 1017759
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710 2 $a University of Southern California. $b Pharmaceutical Sciences. $3 2102227
773 0 $t Dissertation Abstracts International $g 75-02B(E).
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