Abstract
BackgroundThe triblock copolymers PEG-P(Asp-DIP)-P(Lys-Ca) (PEALCa) of polyethylene glycol (PEG), poly(N-(N’,N’-diisopropylaminoethyl) aspartamide) (P(Asp-DIP)), and poly (lysine-cholic acid) (P(Lys-Ca)) were synthesized as a pH-sensitive drug delivery system. In neutral aqueous environment such as physiological environment, PEALCa can self-assemble into stable vesicles with a size around 50-60 nm, avoid uptake by the reticuloendothelial system (RES), and encase the drug in the core. However, the PEALCa micelles disassemble and release drug rapidly in acidic environment that resembles lysosomal compartments.Methodology/Principal FindingsThe anticancer drug Paclitaxel (PTX) and hydrophilic superparamagnetic iron oxide (SPIO) were encapsulated inside the core of the PEALCa micelles and used for potential cancer therapy. Drug release study revealed that PTX in the micelles was released faster at pH 5.0 than at pH 7.4. Cell culture studies showed that the PTX-SPIO-PEALCa micelle was effectively internalized by human colon carcinoma cell line (LoVo cells), and PTX could be embedded inside lysosomal compartments. Moreover, the human colorectal carcinoma (CRC) LoVo cells delivery effect was verified in vivo by magnetic resonance imaging (MRI) and histology analysis. Consequently effective suppression of CRC LoVo cell growth was evaluated.Conclusions/SignificanceThese results indicated that the PTX-SPION-loaded pH-sensitive micelles were a promising MRI-visible drug release system for colorectal cancer therapy.
Highlights
Colorectal carcinoma (CRC) is a malignant disease on the rise
Conclusions/Significance: These results indicated that the PTX-SPION-loaded pH-sensitive micelles were a promising MRIvisible drug release system for colorectal cancer therapy
The amount of released drug is a key for chemotherapeutic agents to efficiently kill the cancer cells and studies involving rapid and adequateh intracellular drug release from nanocarriers are of particular importance at present
Summary
Colorectal carcinoma (CRC) is a malignant disease on the rise. It is the second most common cancer in general and the most common of the gastrointestinal tract cancers [1]. Its use has remained limited due to this unsatisfactory therapeutic efficacy [7] In comparison, nanoparticles, such as cationic polymers and cationic peptides loaded with anti-tumor drugs, have potential to overcome these shortcomings. Nanocarriers with a triggered release mechanism have been developed, such as micelles which could release drugs in response to specific stimuli such as temperature, pH, PLOS ONE | www.plosone.org pH-Sensitive Nanomicelles for CRC ultrasound and redox potential, etc [9,10,11,12] Among these carriers, pH-sensitive polymers appears to be the most attractive candidate because the smart delivery systems are stable and can self-assemble in physiological environment (blood, pH = 7.4) but dessembles and releases drug in acidic environments (lysosomal, pH = 5.0), resulting in significantly enhanced anti-tumor efficacy, minimal drug resistance and side effects [13,14]. Our study attempts to explore the transferring efficiency of PTXPEALCa into tumoral cells and and compare the degree of human CRC LoVo cell growth suppression between PTX-PEALCa with conventional anti-cancer drugs
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