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)

Hydrophilic, fluorescent hybrid nanoprobes (NDI@HNPs) encapsulated with the hydrophobic pH-responsive fluorophore (N,N'-di-n-dodecyl-2,6-di(4-methyl-piperazin-1-yl)naphthalene-1,4,5,8-tetracarboxylic acid diimide, NDI) for recognizing and mapping the route of cell phagocytosis have been fabricated based on the self-assembly of amphiphilic diblock copolymer PS-b-PAA and the subsequent shell cross-linking with 3-mercaptopropyltrimethoxy silane (MPTMS). The as-synthesized NDI@HNPs has a typical spherical morphology of 46 nm in diameter with excellent monodispersity in aqueous solution. The NDI@HNPs probe exhibits extremely low cytotoxicity, fast real time pH response and enhanced fluorescence intensity under acidic environment with respect to the corresponding free dye in highly polar aqueous system because of the encapsulation of NDI molecules inside nanoparticle cores with weak polarity environment. The fluorescence intensity of NDI@HNPs is enhanced by 55-fold upon changing from neutral (pH = 7.4) or basic (pH = 8.4) to acid (pH = 3.4) in aqueous system, in contrast to the serious fluorescence quenching of free NDI in the same medium, which can exactly meet the physiological pH range in cells. The favorably long emission wavelength is beneficial to the low scattering and minimal interfering requirements to fluorescent bioimaging. Moreover, functionalization with rapid cell-penetrating peptides (HIV-1 TAT) allows them to overcome the physiological and biological barriers during the phagocytosis process. Its characteristic fluorescent response to pH benefits the intracellular labeling and organelle targeting, realizing the real time tracking of the probe entry into cancer cells, the accumulation into the endolysosome and the further escape.
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PMID:A pH-responsive hybrid fluorescent nanoprober for real time cell labeling and endocytosis tracking. 2409 49

The cargo-loaded mesoporous silica nanoparticles (MSNs) with convenient surface modification can facilitate the development of the innovative nanodrug system. Herein, the present investigation described the electrostatically self-assembled MSNs as a nanosized drug carrier to realize potent synergistic chemotherapy based on the specificity in targeting cytoplasm and nucleus of tumor cells. In this context, the primarily constructed MSNs were subjected with anticancer drug topotecan (TPT) into its large pores. Then, the selective TAT peptide (a nuclear localization signal peptide) was anchored onto TPT-loaded MSNs (TPT-MSN). Subsequently, the positive surface of TPT-MSN-TAT was capped with negatively charged components, poly(acrylic acid) (PAA)-cRGD peptide and citraconic anhydride (CAH)-metformin (MT), and acted as a smart gatekeeper. Comparatively, PAA-cRGD attached onto MSNs serving as the targeted molecules could upsurge by invasion into cancer cells. Interestingly, the acidic pH of the lysosomal compartment in tumor cells triggers the conjugated CAH from the polymer decorated mesoporous silica (PMS) nanocomposite and could efficiently release MT into the cytoplasm. Consequently, the remaining TPT-MSN-TAT efficiently targets the nucleus and delivers the TPT to improve synergistic chemotherapeutic effects. The precisely released drugs were individually enhanced in the in vitro and in vivo cell killing efficiencies. Thus, the study provides a potential drug delivery podium through combined drugs to realize cancer cell targeting approach.
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PMID:Cancer Therapeutic Proficiency of Dual-Targeted Mesoporous Silica Nanocomposite Endorses Combination Drug Delivery. 3002 69