Abstract
Targeted drug delivery could increase the efficacy of chemotherapy, however, a plethora of obstacles exist in the current targeted delivery designs. In this study, we introduce a novel avenue of targeted drug delivery using electro-acupuncture and evaluate its effect on the distribution of paclitaxel in a breast cancer mouse model. Our results show that electro-acupuncture intervention significantly increased the intratumoral concentration of paclitaxel. The mice in acupuncture group showed shorter tmax, longer t1/2 and higher AUC of paclitaxel as compared with that in paclitaxel-only group. Moreover, we found that the acupuncture intervention significantly induced cell apoptosis in tumors. The levels of COL IV and α-SMA increased in tumors of acupuncture group. The negative tumor metastasis biomarker, NM23, was significantly upregulated in tumors of mice in acupuncture group. Our results suggest that acupuncture intervention around the tumor area increases the local concentration of chemotherapeutic agents. The targeted effect of acupuncture is achieved by altering tumor microvasculature and microenvironment. Therefore, combined therapy of acupuncture with chemotherapeutic agents is promising in improving cancer treatment efficacy.
Highlights
The goal of targeted drug delivery system (TDDS) is to deliver a certain amount of a therapeutic agent to a targeted diseased area within the body
What’s more, there were no significant differences in paclitaxel pharmacokinetic parameters in lung, liver, spleen, kidney, and heart between tumor group (TG) group and electro-acupuncture tumor group (EATG) group (Supplementary Table S1; Supplementary Figure S4)
We found that the fluorescence intensity within tumor area was higher in electro-acupuncture group than that in control group after cy7-paclitaxel injection in several time points
Summary
The goal of targeted drug delivery system (TDDS) is to deliver a certain amount of a therapeutic agent to a targeted diseased area within the body. Tumor-targeted drug delivery system has showed great potential in cancer therapy. Cytotoxic chemotherapy is the major treatment choice used for triple-negative breast cancer [5]. Increasing the intratumoral drug concentration is critical for improving the efficacy of chemotherapy in triple negative breast cancer. Acupuncture has been used in China for thousands of years as an important part of traditional Chinese medicine [7]. It has been accepted and used by at least 103 countries according to the WHO statistics [8]. We perform in vivo imaging and pharmacokinetic analysis to examine whether acupuncture intervention could alter the distribution of paclitaxel in triple negative breast cancerbearing mice. We further explored whether acupuncture could change the tumor microvasculature and microenvironment in molecular level
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