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Optimizing molecular weight of octyl chitosan as drug carrier for improving tumor therapeutic efficacy.

ABSTRACT: Macromolecular drug carriers have attracted much attention taking advantage of passive tumor targeting property and excellent biocompatibility. For many biomedical applications, however, the effectiveness of the carriers is insufficient, which complicate further development into clinical use. Here, we systematically investigated the effects of molecular weight (from 1KDa to 300KDa) of macromolecular drug carrier, octyl chitosan, on tumor accumulation and penetration, as well as drug loading and releasing profiles. It was found that the molecular weight of chitosan influenced the cellular uptake and pharmacokinetic behavior of the nanocarriers, which ultimately determined their drug delivery efficiency. Interestingly, increased molecular weight of chitosan decreased its cellular uptake but increased its resident time in blood, which provided ample time for tumor accumulation. Moreover, the molecular weight altered the drug loading capability and release profile. Our results demonstrated that 10KDa octyl chitosan was an ideal candidate for anticancer drug delivery, which could deliver anticancer agent to tumor tissues and release drugs in tumor cells more effectively than those of other molecular weights, and finally result in better therapeutic effect.

SUBMITTER: Zhang M

PROVIDER: S-EPMC5609998 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Magnetic hyperthermia (MH) has been introduced clinically as an alternative approach for the focal treatment of tumors. MH utilizes the heat generated by the magnetic nanoparticles (MNPs) when subjected to an alternating magnetic field (AMF). It has become an important topic in the nanomedical field due to their multitudes of advantages towards effective antitumor therapy such as high biosafety, deep tissue penetration, and targeted selective tumor killing. However, in order for MH to progress and to realize its paramount potential as an alternative choice for cancer treatment, tremendous challenges have to be overcome. Thus, the efficiency of MH therapy needs enhancement. In its recent 60-year of history, the field of MH has focused primarily on heating using MNPs for therapeutic applications. Increasing the thermal conversion efficiency of MNPs is the fundamental strategy for improving therapeutic efficacy. Recently, emerging experimental evidence indicates that MNPs-MH produces nano-scale heat effects without macroscopic temperature rise. A deep understanding of the effect of this localized induction heat for the destruction of subcellular/cellular structures further supports the efficacy of MH in improving therapeutic therapy. In this review, the currently available strategies for improving the antitumor therapeutic efficacy of MNPs-MH will be discussed. Firstly, the recent advancements in engineering MNP size, composition, shape, and surface to significantly improve their energy dissipation rates will be explored. Secondly, the latest studies depicting the effect of local induction heat for selectively disrupting cells/intracellular structures will be examined. Thirdly, strategies to enhance the therapeutics by combining MH therapy with chemotherapy, radiotherapy, immunotherapy, photothermal/photodynamic therapy (PDT), and gene therapy will be reviewed. Lastly, the prospect and significant challenges in MH-based antitumor therapy will be discussed. This review is to provide a comprehensive understanding of MH for improving antitumor therapeutic efficacy, which would be of utmost benefit towards guiding the users and for the future development of MNPs-MH towards successful application in medicine.

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Optimizing molecular weight of octyl chitosan as drug carrier for improving tumor therapeutic efficacy.

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