Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The particle shape of the drug delivery systems had a strong impact on their in vitro and in vivo performance, but there was limited availability of techniques to produce the specific shaped drug carriers. In this article, the novel methotrexate (MTX) decorated MPEG-PLA nanobacillus (MPEG-PLA-MTX NB) was prepared by the self-assembly technique followed by the extrusion through SPG membrane with high N2 pressure for targeted drug delivery, in which Janus-like MTX was not only used as a specific anticancer drug but could also be served as a tumor-targeting ligand. The MPEG-PLA-MTX NBs demonstrated much higher in vitro and in vivo targeting efficiency compared to the MPEG-PLA-MTX nanospheres (MPEG-PLA-MTX NSs) and MPEG-PLA nanospheres (MPEG-PLA NSs). In addition, the MPEG-PLA-MTX NBs also displayed much more excellent in vitro and in vivo antitumor activity than the MPEG-PLA-MTX NSs and free MTX injection. To our knowledge, this work provided the first example of the integration of the shape design (which mediated an early phase tumor accumulation and a late-phase cell internalization) and Janus-faced function (which mediated an early phase active targeting effect and a late-phase anticancer effect) on the basis of nanoscaled drug delivery systems. The highly convergent and cooperative drug delivery strategy opens the door to more drug delivery systems with new shapes and functions for cancer therapy.
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PMID:Bacillus-shape design of polymer based drug delivery systems with janus-faced function for synergistic targeted drug delivery and more effective cancer therapy. 2571 May 90

Poor drug distribution and inefficient drug concentrations within the tumor intracellular environment still limit the therapeutic efficacy of drugs for cancer chemotherapy. Local drug delivery (physical targeting) combined with receptor-mediated drug delivery (chemical targeting) and assistance by a novel shape design is a promising strategy to treat the infiltrating tumor (even those that persist post surgery). In this paper, we prepared dye and methotrexate (MTX) functionalized nanobacilli (MPEG-PLA-MTX-Cy5.5 NB) by a self-assembly technique combined with extrusion through a SPG membrane for intratumoral administration, in which the bacillus-shaped MPEG-PLA-MTX-Cy5.5 NB were armed with a dual-acting MTX that can specifically and efficiently enhance their cellular uptake, while avoiding their dispersion from tumor sites. After intratumoral administration to a H22 xenograft mouse model, the MPEG-PLA-MTX-Cy5.5 NB delivered the drug more effectively to the tumor compared to the MPEG-PLA-Cy5.5 nanospheres (MPEG-PLA-Cy5.5 NSs) and MPEG-PLA-MTX-Cy5.5 nanospheres (MPEG-PLA-MTX-Cy5.5 NSs). Compared to the free MTX and MPEG-PLA-MTX-Cy5.5 NSs, the controlled-release MPEG-PLA-MTX-Cy5.5 NB also significantly inhibited the tumor growth and improved therapeutic efficacy. The platforms are highly convergent, flexible and simplified systems that may serve as guides in the further design of nanoparticles with a revolutionary new shape and function for clinical applications.
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PMID:Self-targeted, bacillus-shaped, and controlled-release methotrexate prodrug polymeric nanoparticles for intratumoral administration with improved therapeutic efficacy in tumor-bearing mice. 3226 80