Abstract
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Objectives: Early detection treatment effect is very helpful for in vivo evaluation of drug potential and clinical doctors to adjust the therapeutic regimen in time.
Methods: In this study, a dual targeted nanodrug, hyaluronic acid nanoparticles (HANPs) encapsulated with paclitaxel (PTX), were investigated. Preclinically, PTX-loaded HANPs (HANP/PTX) showed dose-dependent cytotoxicity to cancer cells (HT29, A549, MDA-MB-231, HepG2 and MDA-MB-435s) and significantly lower cytotoxicity against normal fibroblasts (NIH-3T3) than free PTX. In vivo, we administered PBS, free paclitaxel, paclitaxel protein-bound particles (Abraxane) and HANPs/PTX through vena caudalis to each group of athymic nude mice with MDA-MB-435s tumors. To monitor therapeutic responses, we performed positron emission tomography (PET) imaging, in sessions that lasted 90 mins, starting with injection via the tail vein catheters with 18F-FDG 40 mins later. Animal studies were carried out under a protocol approved by the National Institutes of Health Clinical Center Animal Care and Use Committee (CC/ACUC, Protocol # NIBIB 13-03). Results: As expected, the control group, treated with saline and free PTX, exhibited a rapid increase in tumor size as a function of time. No significant increase in tumor size was found for the group treated with HANPs/PTX or Abraxane. On HANPs/PTX treatment, the tumor uptake of 18F-FDG is less than the untreated tumors’ in a day-3 to day-0 ratio (0.86:1.18). Conclusion: Overall, HANP/PTX with well water-solubility and a decrease of toxic side effects showed promising potential as a dual targeted drug carrier for cancer therapy. 18F-FDG PET can be used for early detection treatment effect to monitoring therapeutic responses. Our research can provide the basis for the clinical transformation of medicine.