Dual responsive PNIPAM–chitosan targeted magnetic nanopolymers for targeted drug delivery (original) (raw)

Thermal and pH Responsive Polymer-Tethered Multifunctional Magnetic Nanoparticles for Targeted Delivery of Anticancer Drug

ACS Applied Materials & Interfaces, 2013

Targeted and efficient delivery of therapeutics to tumor cells is one of the key issues in cancer therapy. In the present work, we report a temperature and pH dual responsive core−shell nanoparticles comprising smart polymer shell coated on magnetic nanoparticles as an anticancer drug carrier and cancer cell-specific targeting agent. Magnetite nanoparticles (MNPs), prepared by a simple coprecipitation method, was surface modified by introducing amine groups using 3-aminopropyltriethoxysilane. Dual-responsive poly(N-isopropylacrylamide)-block-poly-(acrylic acid) copolymer, synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization, was then attached to the amine-functionalized MNPs via EDC/NHS method. Further, to accomplish cancer-specific targeting properties, folic acid was tethered to the surface of the nanoparticles. Thereafter, rhodamine B isothiocyanate was conjugated to endow fluorescent property to the MNPs required for cellular imaging applications. The nanoparticles were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), selected area electron diffraction (SAED), field emission scanning electron microscopy (FESEM), energy-dispersive X-ray spectroscopy (EDX), thermogravimetric analysis (TGA), zeta potential, vibrating sample magnetometer (VSM), X-ray photoelectron spectroscopy (XPS) measurements, and FTIR, UV−vis spectral analysis. Doxorubicin (DOX), an anticancer drug used for the present study, was loaded into the nanoparticles and its release behavior was subsequently studied. Result showed a sustained release of DOX preferentially at the desired lysosomal pH and temperature condition. The biological activity of the DOX-loaded MNPs was studied by MTT assay, fluorescence microscopy, and apoptosis. Intracellular-uptake studies revealed preferential uptake of these nanoparticles into cancer cells (HeLa cells) compared to normal fibroblast cells (L929 cells). The in vitro apoptosis study revealed that the DOX-loaded nanoparticles caused significant death to the HeLa cells. These nanoparticles were capable of target specific release of the loaded drug in response to pH and temperature and hence may serve as a potential drug carrier for in vivo applications.

Multi-functional magnetic nanoparticles as an effective drug carrier for the controlled anti-tumor treatment

Journal of biomaterials applications, 2018

Because of the complications and mutability of cancers, combination of chemotherapy and other therapy with multi-mechanisms would be a bright future for the treatment of cancer. Thus, development of multi-functional tumor-targeted drug delivery systems with two or more than two functions should be of great significance. In the study, the FeO@C nanoparticles linked with thermoresponsive copolymer (MTC-NPs) were synthesized, after that, the magnetic properties and photothermal effects of MTC NPs were evaluated. Compared to the pure water, MTC-NPs absorbed more energy and transform it into heat under the 808 nm laser irradiation, and the temperature could increase over 60℃. In addition, the grafted copolymer with coil-to-globule transition acts as a gatekeeper for the temperature-controlled release of mitoxantrone molecules. The super paramagnetic behavior of MTC-NPs certified by the hysteresis loop gives a negligible coercivity at room temperature. Both in vitro and in vivo studies co...

Magnetic Nanoparticles as Versatile Carrier for Anti-Cancer Drug Delivery

The objective of this study is to develop a passive targeting of multilayered nanoparticles encountering multiple obstacles on the way to their target due to the mucosal barrier, nonspecific uptake of the drug. To prevent the nonspecific drug toxicity and combination chemotherapy for synergistic effect, multifunctional ferromagnetic properties were successfully fabricated by the layer-by-layer assembly (LBL) technique. The drug-loaded magnetic chitosan nanospheres were coated alternatively with sodium alginate and chitosan up to 3 layers incorporated with melphalan and methotrexate. The core-shell type composites consisting of magnetic nanoparticles decorated with biological substances are interesting for various biomedical applications. The magnetic property investigation reveals that drug-loaded nanomaterials exhibit superparamagnetic behavior. The uniformly distributed magnetic nanoparticles were also observed in scanning electron microscopic images to characterize the synthesized product. The thin film consisting of chitosan nanospheres was coated alternatively with sodium alginate and magnetic nanoparticles had a conductivity of two formulations F1a and F2a were 35.2 emu/g and 43.4 emu/g respectively. The formulation was evaluated for its particle size, size distribution, zeta potential, and in-vitro drug release in the pH of 1.2 and 7.0 fitted in kinetic release studies. The developed magnetic nanoparticles showed promising results with betterdelayed drug action and will be an enhanced therapeutic means in combating the infections of cancer therapy.

Magnetically active pNIPAM nanosystems as temperature-sensitive biocompatible structures for controlled drug delivery

Artificial Cells, Nanomedicine, and Biotechnology, 2020

Here, temperature-sensitive hybrid poly(N-isopropylacrylamide) (pNIPAM) nanosystems with magnetic response are synthesised and investigated for controlled release of 5-fluorouracil (5FU) and oxaliplatin (OXA). Initially, magnetic nanoparticles (@Fe 3 O 4) are synthesised by co-precipitation approach and functionalised with acrylic acid (AA), 3-butenoic acid (3BA) or allylamine (AL) as comonomers. The thermoresponsive polymer is grown by free radical polymerisation using N-isopropylacrylamide (NIPAM) as monomer, N,N'-methylenbisacrylamide (BIS) as cross-linker, and 2,2'-azobis(2-methylpropionamidene) (V50) as initiator. We evaluate particle morphology by transmission electron microscopy (TEM) and particle size and surface charge by dynamic light scattering (DLS) and Z-potential (ZP) measurements. These magnetically active pNIPAM@ nanoformulations are loaded with 5-fluorouracil (5FU) and oxaliplatin (OXA) to determine loading efficiency, drug content and release as well as the cytotoxicity against T-84 colon cancer cells. Our results show high biocompatibility of pNIPAM nanoformulations using human blood cells and cultured cells. Interestingly, the pNIPAM@Fe 3 O 4-3BA þ 5FU nanoformulation significantly reduces the growth of T-84 cells (57% relative inhibition of proliferation). Indeed, pNIPAM-co-AL@Fe 3 O 4-AA nanosystems produce a slight migration of HCT15 cells in suspension in the presence of an external magnetic field. Therefore, the obtained hybrid nanoparticles can be applied as a promising biocompatible nanoplatform for the delivery of 5FU and OXA in the improvement of colon cancer treatments.

Curcumin and 5-Fluorouracil-loaded, folate- and transferrin-decorated polymeric magnetic nanoformulation: a synergistic cancer therapeutic approach, accelerated by magnetic hyperthermia

International Journal of Nanomedicine, 2014

The efficient targeting and therapeutic efficacy of a combination of drugs (curcumin and 5-Fluorouracil [5FU]) and magnetic nanoparticles encapsulated poly(D,L-lactic-co-glycolic acid) nanoparticles, functionalized with two cancer-specific ligands are discussed in our work. This multifunctional, highly specific nanoconjugate resulted in the superior uptake of nanoparticles by cancer cells. Upon magnetic hyperthermia, we could harness the advantages of incorporating magnetic nanoparticles that synergistically acted with the drugs to destroy cancer cells within a very short period of time. The remarkable multimodal efficacy attained by this therapeutic nanoformulation offers the potential for targeting, imaging, and treatment of cancer within a short period of time (120 minutes) by initiating early and late apoptosis.

Magnetic nanobeads decorated by thermo-responsive PNIPAM shell as medical platforms for the efficient delivery of doxorubicin to tumour cells

Nanoscale, 2011

Medical nanoplatforms based on clusters of superparamagnetic nanoparticles decorated with a PNIPAM thermo-responsive shell have been synthesized and used as drug carriers for doxorubicin (DOXO), a common chemotherapeutic agent. The nanosystem here developed has a total diameter below 200 nm and exploits the temperature responsive behaviour of the PNIPAM polymeric shell for the controlled loading and release of DOXO. The system has been tested in vitro on tumour cells and it clearly demonstrates the effectiveness of drug polymer encapsulation and time-dependent cell death induced by the doxorubicin release. Comparative cellular studies of the DOXO loaded nanoplatform in the presence or absence of an external magnet (0.3 T) showed the synergic effect of accumulation and enhanced toxicity of the system, when magnetically guided, resulting in the enhanced efficacy of the system. ; Fax: +39 0832 298 230; Tel: +39 0832 298 214 b National Nanotechnology Laboratory of CNR-NANO, via per Arnesano km 5, 73100 Lecce, Italy † Electronic supplementary information (ESI) available: A table summarizing the DOXO loading parameters, DLS of some steps of the reaction and additional TEM characterization images of the DOXO loaded nanobeads, and additional TEM characterization of cells treated with the nanobeads. See

Hyaluronic Acid-Modified Cisplatin-Encapsulated Poly(Lactic-co-Glycolic Acid) Magnetic Nanoparticles for Dual-Targeted NIR-Responsive Chemo-Photothermal Combination Cancer Therapy

Pharmaceutics

Combination chemo-photothermal therapy with nanomaterials can reduce the dose of chemotherapeutic drugs required for effective cancer treatment by minimizing toxic side effects while improving survival times. Toward this end, we prepare hyaluronic acid (HA)-modified poly(lactic-co-glycolic acid) (PLGA) magnetic nanoparticles (MNP) for the CD44 receptor-mediated and magnetic field-guided dual-targeted delivery of cisplatin (CDDP). By co-encapsulating the CDDP and oleic acid-coated iron oxide MNP (IOMNP) in PLGA, the PMNPc was first prepared in a single emulsification/solvent evaporation step and successively surface modified with chitosan and HA to prepare the HA/PMNPc. Spherical HA/PMNPc nanoparticles of ~300 nm diameter can be prepared with 18 and 10% (w/w) loading content of CDDP and IOMNP and a pH-sensitive drug release to facilitate the endosomal release of the CDDP after intracellular uptake. This leads to the higher cytotoxicity of the HA/PMNPc toward the U87 glioblastoma cell...

Chitosan nanoparticles for combined drug delivery and magnetic hyperthermia: From preparation to in vitro studies

Carbohydrate Polymers, 2017

 Chitosan nanoparticles (CSNPs) were prepared through crosslinking with tripolyphosphate salts  Magnetic nanoparticles and 5-fluorouracyl (5-FU) were encapsulated within CSNPs  5-FU release measured after 30 days decreases with magnetic nanoparticles content  CSNPs were successfully internalized over fibroblasts and A-172 cancer cells  CSNPs induced cell apoptosis by combination of magnetic hyperthermia and chemotherapy ABSTRACT Chitosan nanoparticles (CSNPs) ionically crosslinked with tripolyphosphate salts (TPP) were employed as nanocarriers in combined drug delivery and magnetic hyperthermia (MH) therapy. To that aim, three different ferrofluid concentrations and a constant 5fluorouracil (5-FU) concentration were efficiently encapsulated to yield magnetic CSNPs with core-shell morphology. In vitro experiments using normal cells, fibroblasts (FHB) and cancer cells, human glioblastoma A-172, showed that CSNPs presented a dose-dependent cytotoxicity and that they were successfully uptaken into both cell lines. The application of a MH treatment in A-172 cells resulted in a cell viability of 67-75% whereas no significant reduction of cell viability was observed for FHB. However, the A-172 cells showed re-growth populations 4 hours after the application of the MH treatment when CSNPs were loaded only with ferrofluid. Finally, a combined effect of MH and 5-FU release was observed with the application of a second MH treatment for CSNPs exhibiting a lower amount of released 5-FU. This result demonstrates the potential of CSNPs for the improvement of MH therapies.

Development of Multiple Stimuli Responsive Magnetic Polymer Nanocontainers as Efficient Drug Delivery Systems

Macromolecular Bioscience, 2013

Magnetic nanodevices based on poly[(methacrylic acid)-co-(N-isopropylacrylamide)] [P(MAAco-NIPAAm)] are prepared and used as drug delivery systems employing daunorubicin (DNR) as a model drug. The magnetic nanocontainers exploit the pH, temperature, and magnetic response of the polymeric shell constituents and magnetic nanoparticles, respectively, for controlled pH, temperature and alternating magnetic field triggered drug release. The in vitro cytotoxicity of both DNR-loaded and empty nanocontainers is examined on MCF-7 breast cancer cells along with the intracellular distribution of DNR. The results show that the DNRloaded nanocontainers have an anti-tumor effect comparable to the free drug. The current observations provide important information for potent drug delivery and release systems.

Synthesis and evaluation of multi layered magnetic nanoparticles as versatile carrier for anti-cancer drug delivery.

International Journal of Life Sciences and Pharmaceutical Research., 2020

The objective of this study is to develop a passive targeting of multilayered nanoparticles encountering multiple obstacles on the way to their target due to the mucosal barrier, nonspecific uptake of the drug. To prevent the nonspecific drug toxicity and combination chemotherapy for synergistic effect, multifunctional ferromagnetic properties were successfully fabricated by the layer-by-layer assembly (LBL) technique. The drug-loaded magnetic chitosan nanospheres were coated alternatively with sodium alginate and chitosan up to 3 layers incorporated with melphalan and methotrexate. The core-shell type composites consisting of magnetic nanoparticles decorated with biological substances are interesting for various biomedical applications. The magnetic property investigation reveals that drug-loaded nanomaterials exhibit superparamagnetic behavior. The uniformly distributed magnetic nanoparticles were also observed in scanning electron microscopic images to characterize the synthesized product. The thin film consisting of chitosan nanospheres was coated alternatively with sodium alginate and magnetic nanoparticles had a conductivity of two formulations F1a and F2a were 35.2 emu/g and 43.4 emu/g respectively. The formulation was evaluated for its particle size, size distribution, zeta potential, and in-vitro drug release in the pH of 1.2 and 7.0 fitted in kinetic release studies. The developed magnetic nanoparticles showed promising results with better-delayed drug action and will be an enhanced therapeutic means in combating the infections of cancer therapy.