Chitosan-based intelligent theragnosis nanocomposites enable pH-sensitive drug release with MR-guided imaging for cancer therapy

Abstract

Smart drug delivery systems that are triggered by environmental conditions have been developed to enhance cancer therapeutic efficacy while limiting unwanted effects. Because cancer exhibits abnormally high local acidities compared to normal tissues (pH 7.4) due to Warburg effects, pH-sensitive systems have been researched for effective cancer therapy. Chitosan-based intelligent theragnosis nanocomposites, N-naphthyl-O-dimethymaleoyl chitosan-based drug-loaded magnetic nanoparticles (NChitosan-DMNPs), were developed in this study. NChitosan-DMNPs are capable of pH-sensitive drug release with MR-guided images because doxorubicin (DOX) and magnetic nanocrystals (MNCs) are encapsulated into the designed N-naphthyl-O-dimethymaleoyl chitosan (N-nap-O-MalCS). This system exhibits rapid DOX release as acidity increases, high stability under high pH conditions, and sufficient capacity for diagnosing and monitoring therapeutic responses. These results demonstrate that NChitosan-DMNPs have potential as theragnosis nanocomposites for effective cancer therapy.

pH‐Responsive Drug‐Delivery Systems

“…The overall drug release rate was much higher at a lower pH range (pH 2-5) and negligible drug release was observed at physiological pH. [87] Lim et al [88] reported chitosan-based intelligent theragnosis nanocomposites, N-naphthyl-O-dimethymaleoyl chitosan-based drug-loaded magnetic nanoparticles, which were capable of pH-sensitive drug release with magnetic resonance-guided imaging. This drug-delivery system exhibited rapid DOX release in an acidic environment; N-naphthyl-O-dimethymaleoyl chitosan-based drug-loaded magnetic nanoparticles in a solution at pH 9.8 showed particle sizes of approximately (100.3 AE 4.9) nm, but their sizes increased slightly with increased buffer solution acidity ((185.3 AE 13.5) nm at pH 5.5 and (158.8 AE 10.6) nm at pH 7.4; see Figure 11a).…”

Systems for the delivery of chemotherapeutic drugs, new approaches and perspective

“…There is a tremendous opportunity to get a new drug delivery systems using nanotechnology, the benefits of nano products [1,3,4,19,20,22,62,82,[84][85][86][87] are: i) protecting the drug from premature degradation (increases drug stability, reduces degradation and maximizes drug action) [1]; ii) preventing drugs from early interaction with the biological environment [1]; iii) increasing drug absorption in specific tissues (e.g., solid tumors) [1,15,20]; iv) controling the pharmacokinetics properties of the drug and its tissue distribution [1,15,20,22,85,88]; v) improving intracellular penetration [22,28,88]; vi) overcome tumors multi-drug resistant (magnetic nanoparticles, immunoliposomes, nanoliposomes, etc.) [4,19,60,[89][90][91].…”

“…Magnetic targeted delivery of drugs (MDT) was introduced by Kenneth J. Widder et al [114] for specific targeting delivery of Adriamycin-loaded magnetic albumin microspheres. Magnetic liposomes and the magnetic nanoparticles have been used for a broad range of biomedical and diagnostic applications, such as determination of cell growth, magnetic resonance imaging (MRI), magnetic hyperthermia [91,110,112,115,116] and localized targeting drugs delivery [15,85,90,91,117]. In research conducted by Suman Dandamudi et al [112] was shown in vivo that magnetic field improves vascular absorption of vinblastine encapsulated magnetic cationic liposomes (MCLs-VLB) in tumors and significantly increases the cytotoxic activity against B16-F10 tumor cells.…”

“…The coating of magnetic nanoparticles with polymers is the most common method for developing a magnetic targeting drug delivery system and diagnostic tools. Moreover, it allows to improve the stability of the nanoparticles from oxidation in the body and may provide certain properties to the nanocarriers as thermal sensitivity (ex: poly-N-isopropylacrylamide) [1], the pH sensitivity (ex: N-naphthyl-Odimethylmaleoyl chitosan, poly(2-(dimethylamine)ethyl methacrylate (PDMAEMA), polyethylene glycol-ortho esterdistearoyl glycol conjugate (POD) / dioleoylphosphatidylethanolamine (DOPE) [76,85,118], targeted action, etc. Eun-Kyung Lim et al [85] 4.…”

“…Moreover, it allows to improve the stability of the nanoparticles from oxidation in the body and may provide certain properties to the nanocarriers as thermal sensitivity (ex: poly-N-isopropylacrylamide) [1], the pH sensitivity (ex: N-naphthyl-Odimethylmaleoyl chitosan, poly(2-(dimethylamine)ethyl methacrylate (PDMAEMA), polyethylene glycol-ortho esterdistearoyl glycol conjugate (POD) / dioleoylphosphatidylethanolamine (DOPE) [76,85,118], targeted action, etc. Eun-Kyung Lim et al [85] 4. In the work of Lilian Zhou et al [22] developed a simple method for synthesis of magnetic nanoparticles (MNPS) coated with poly-2-dimethylamino-ethyl methacrylate (PDMAEMA) as a new potential carrier for targeted drug delivery with controlled-release.…”