Doxorubicin-Loaded Alginate-g-Poly(N-isopropylacrylamide) Micelles for Cancer Imaging and Therapy

Abstract

Chemotherapy is a widely adopted method for the treatment of cancer. However, its use is often limited due to side effects produced by anti-cancer drugs. Therefore, various drug carriers, including polymeric micelles, have been investigated to find a method to overcome this limitation. In this study, alginate-based, self-assembled polymeric micelles were designed and prepared using alginate-g-poly(N-isopropylacrylamide) (PNIPAAm). Amino-PNIPAAm was chemically introduced to the alginate backbone via carbodiimide chemistry. The resulting polymer was dissolved in distilled water at room temperature and formed self-assembled micelles at 37 °C. Characteristics of alginate-g-PNIPAAm micelles were dependent on the molecular weight of PNIPAAm, the degree of substitution, and the polymer concentration. Doxorubicin (DOX), a model anti-cancer drug, was efficiently encapsulated in alginate-g-PNIPAAm micelles, and sustained release of DOX from the micelles was achieved at 37 °C in vitro. These micelles accumulated at the tumor site of a tumor-bearing mouse model as a result of the enhanced permeability and retention effect. Interestingly, DOX-loaded alginate-g-PNIPAAm micelles showed excellent anti-cancer therapeutic efficacy in a mouse model without any significant side effects. This approach to designing and tailoring natural polymer-based systems to fabricate nanoparticles at human body temperature may provide a useful means for cancer imaging and therapy.

Inhibition of HeLa cell growth by doxorubicin-loaded and tuftsin-conjugated arginate-PEG microparticles

“…In the first solution, the solution was stirred overnight at room temperature and precipitated by centrifugation under 19,750 g for 5 min to remove the leftover PEG and ALG [1] . Then, the solution was loaded into a dialysis bag (MWCO 8000–14000 Da) and dialyzed against distilled water for 2 days to remove residual reagents before obtaining ALG-PEG [10] , [14] . The second solution was incubated for 2 min under magnetic stirring, followed by adding Dox to a final concentration of 1 mg/ml, and then stirred overnight at room temperature.…”

“…In order to further prevent burst release of drug, polymers were employed to modify ALG [4] , [5] , [7] . In recent research, ALG has been modified with different types of polyethylene glycol (PEG) to improve its bioactivity and biocompatibility in emulsification [2] , [5] , [8] , [9] , self-assembled polymeric micelles [10] , microcapsule [11] , hybrid microspheres, and cell microencapsulation [8] , [12] , [13] . PEG-modified ALG in these formulations exhibited improved pharmacokinetic properties of Dox through providing physical encapsulation.…”

Dual pH‐ and thermal‐responsive nanocomposite hydrogels for controllable delivery of hydrophobic drug baicalein

“…synthesized a thermoresponsive copolymer, alginate‐ graft ‐poly( N ‐isopropylacrylamide), and achieved a loading of the hydrophobic drug doxorubicin . This provided a new idea for the loading of hydrophobic drugs in a hydrophilic environment …”

“…18 This provided a new idea for the loading of hydrophobic drugs in a hydrophilic environment. 19 Liposomes, having a hydrophilic head and a hydrophobic tail structure, could form spherical sacs in organic or inorganic solvents. [20][21][22] As is well known, a large amount of water is contained in the body's humoral environment.…”

Synthesis and characterization of mesoporous magnetic nanocomposites wrapped with chitosan gatekeepers for pH-sensitive controlled release of doxorubicin

“…However, standard chemotherapy involves the use of a relatively high dose of drugs in order to efficiently kill cancer cells due to the lack of ability to target cancer cells, which is inevitably associated with numerous negative side effects such as cardiotoxicity and intrinsic or acquired drug resistance of tumors [33][34][35]. Therefore, to develop a novel DOX delivery system is a potential method to inhibit tumor growth while avoiding or minimizing these side effects.…”