Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0267964 (PAA)
 2,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In spite of their high potency and specificity, few protein drugs have advanced to the clinical settings due to lack of safe and efficient delivery vehicles. Here, novel anisamide-decorated pH-sensitive degradable chimaeric polymersomes (Anis-CPs) were designed, prepared, and investigated for efficient and targeted delivery of apoptotic protein, granzyme B (GrB), to lung cancer cells. Anis-CPs were readily prepared with varying Anis surface densities from anisamide end-capped poly(ethylene glycol)-b-poly(2,4,6- trimethoxybenzylidene-1,1,1-tris(hydroxymethyl)ethane methacrylate)-b-poly(acrylic acid) (Anis-PEG-PTTMA-PAA) and PEG-PTTMA-PAA copolymers. Using cytochrome C (CC) as a model protein, Anis-CPs displayed high protein loading efficiencies (40.5-100%) and loading contents (up to 16.8 wt %). CC-loaded Anis-CPs had narrow distribution (PDI 0.04-0.13) and small sizes ranging from 152 to 171 nm, which increased with increasing CC contents. Notably, the release of proteins from Anis-CPs was accelerated under mildly acidic conditions, due to the hydrolysis of acetal bonds in PTTMA. MTT assays showed that GrB-loaded Anis-CPs (GrB-Anis-CPs) displayed high targetability to sigma receptor overexpressing cancer cells such as H460 and PC-3 cells. For example, GrB-Anis-CPs exhibited increasing antitumor efficacy to H460 cells with increasing Anis contents from 0 to 80%. The antitumor activity of GrB-Anis-CPs was significantly reduced upon pretreating H460 cells with haloperidol (a competitive antagonist). Notably, the half-maximal inhibitory concentrations (IC50) of GrB-Anis70-CPs were determined to be 6.25 and 5.94 nM for H460 and PC-3 cells, respectively, which were 2-3 orders of magnitude lower than that of chemotherapeutic drugs, such as paclitaxel. Flow cytometry studies demonstrated that GrB-Anis70-CPs induced widespread apoptosis of H460 cells. The confocal laser scanning microscopy (CLSM) experiments using FITC-labeled CC-loaded Anis-CPs confirmed fast internalization and intracellular protein release into H460 cells. GrB-Anis-CPs with high potency and specificity are particularly interesting for targeted therapy of lung cancers.
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PMID:Anisamide-Decorated pH-Sensitive Degradable Chimaeric Polymersomes Mediate Potent and Targeted Protein Delivery to Lung Cancer Cells. 2593 56

Accurate and effective drug delivery in tumor cells significantly improves the curative effect with high drug delivery efficiency, low toxicity and side effects and has become an urgent demand for anticancer therapy. In this paper, a novel traceable and targeted drug delivery nanosystem (i.e. AuNF-nanocarriers) with high drug encapsulation and pH-controlled release was prepared based on gold nanoflowers (AuNFs) for efficient intracellular SERS imaging-guided chemo-phototherapy. SERS-active flower-like gold nanoparticles with large surface area were synthesized first and then modified with Raman and RGD molecules in sequence to prepare bright, traceable and targeted SERS tags of A549 human lung cancer cells. Furthermore, thiolated-PAA (PAA-SH) was synthesized and utilized for the first time to modify the SERS tags with a layer of negative charges for efficient pH-dependent loading and release of the anticancer drug doxorubicin. Based on the A549 human lung cancer cell model, the availability of the proposed AuNF-nanocarriers for efficient intracellular SERS imaging-guided chemo-phototherapy was studied and the results indicate that the AuNF-based drug delivery system exhibited attractive characteristics such as good stability, efficiency and pH-controlled drug loading and release, traceable and targeted delivery, as well as SERS imaging and chemo-phototherapy functions, and shows great potential for powerful SERS-imaging and as a theranostic candidate for precision nanomedicine that could achieve sensitive and accurate tumor detection and therapy.
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PMID:A gold nanoflower-based traceable drug delivery system for intracellular SERS imaging-guided targeted chemo-phototherapy. 3225 38