Magnetic Driven Nanocarriers for pH-Responsive Doxorubicin Release in Cancer Therapy

Abstract

Doxorubicin is one of the most widely used anti-cancer drugs, but side effects and selectivity problems create a demand for alternative drug delivery systems. Herein we describe a hybrid magnetic nanomaterial as a pH-dependent doxorubicin release carrier. This nanocarrier comprises magnetic iron oxide cores with a diameter of 10 nm, enveloped in a hybrid material made of siliceous shells and ĸ-carrageenan. The hybrid shells possess high drug loading capacity and a favorable drug release profile, while the iron oxide cores allows easy manipulation via an external magnetic field. The pH responsiveness was assessed in phosphate buffers at pH levels equivalent to those of blood (pH 7.4) and tumor microenvironment (pH 4.2 and 5). The nanoparticles have a loading capacity of up to 12.3 wt.% and a release profile of 80% in 5 h at acidic pH versus 25% at blood pH. In vitro drug delivery tests on human breast cancer and non-cancer cellular cultures have shown that, compared to the free drug, the loaded nanocarriers have comparable antiproliferative effect but a less intense cytotoxic effect, especially in the non-cancer cell line. The results show a clear potential for these new hybrid nanomaterials as alternative drug carriers for doxorubicin.

Chitosan overlaid Fe3O4/rGO nanocomposite for targeted drug delivery, imaging, and biomedical applications

“…The faster pure DOX release behavior at acidic condition was detected, which was pH-dependent, in which the release value was 25% at pH 7.4 and 81% at pH 5.5. Such a pH-responsive property of MNDC can be practically utilized as a controlled release system, which can gently release doxorubicin in the cancer cell because the pH of intracellular is lower than healthy cells 39 . Under the two different pH conditions, the cumulative drug release prominently occurred at 10 h, and maximum (96.6% and 10%) drug release was achieved at pH 5.5 and at pH 7.4, respectively.…”

Targeted SPION siderophore conjugate loaded with doxorubicin as a theranostic agent for imaging and treatment of colon carcinoma

“…The high dose infusion, adverse effects, low bioavailability, low therapeutic index, and non-specific targeting are some of the major drawbacks of chemotherapy 38 , 39 . In this line, the nonselective distribution of DOX in the normal organs leads to severe systemic toxicity especially cardiotoxicity, which limits localization of free DOX in target tumor site 40 , 41 . In previous attempts to overcome these limitations, the nano-sized aptamer-targeted systems loaded with DOX could improve the biodistribution and antitumor efficacy compared with free DOX 42 , 43 .…”

Remote control of magnetic nanocomplexes for delivery and destruction of cancer cells

“…Comparing the release rates at pH 4.2, 5.0, 7.4, it was shown that the acidic tumor microenvironment assisted targeted DX delivery and thus had more pronounced cytotoxicity than Fe 3 O 4 MCs at pH 7.4 in MCF-7 and MDA-MB-231 cancer cell lines. 60 Likewise, charge reversal was demonstrated in polypeptide nanocomplexes delivering cisplatin to HeLa cells. 61 After being exposed to EFs, MCs based on Fe 3 O 4 nanoparticles and p53 gene resulted in enhanced antitumor effects against the C6 glioma model in vitro and in vivo .…”