br hindering transdermal drug delivery acts as a barrier Con
hindering transdermal drug delivery acts as a barrier. Consequently, transdermal and permeation enhancement technology have been ac-tively studied in attempt to bypass the stratum corneum barrier and enhance transdermal drug delivery [11,12].
Bacterial cellulose (BC) was produced through static fermentation of Acetobacter xylinum. Which has a nano-sized nanofiber with diameters of 30–100 nm [13–16]. When BC is composited with other polymers, the light-scattering from a mismatched refractive index could be neg-ligible as the nano-scale eﬀect. Another advantage is its toughness which can be folded up to 180◦ without fracture, even at fiber contents as low as 5 wt% [17–19].
Hydrogels are consisted of hydrophilic polymer chains which was a water-swollen polymeric materials with a three dimensional (3D) net-work structure. Thus, they can be used for drug delivery by eﬃciently loading drugs in the network as the hydrodynamic properties similar to the biological tissues. They are suitable for facilitate the skin permea-tion of drugs at topical application via skin hydration. Meanwhile, they have been employed for transdermal delivery of other systerms such as liposomes, micelles, nanoparticles [5,10,20,21].
Fe3O4 nanoparticles have attracted considerable attention due to their applications in targeted drug/gene delivery [22-24]. In addition, some studies have proved that magnetic nanoparticles could act as an eﬃcient carrier for cancer treatment [25,26]. But, such magnetic na-noparticles are mostly prepared without modification, which might cause the possible ensuing toxicity. Therefore, it is extremely important and necessary to develop novel magnetic nanoparticles with appro-priate modification properties against cancer Pifithrin-α (PFTα) both in vitro and in vivo [27–32].
Among the above cancer treatment approaches, photodynamic therapy (PDT), is an attractive method to cancer therapies which is a local minimally invasive treatment, easy controllability applicability, and low side eﬀects. In several studies, PDT has been shown to treat superficial cancers such as breast cancer, and is also currently being tested in clinical studies for the treatment of superficial head, neck, and lung cancers. Photosensitizers are released to cancer tissues by in-travenously or orthotopic injection; the cancer tissues are irradiated by corresponding laser with the nanoparticle to generate considerable singlet oxygen to facilitate oxidative damage [33–35].
In the present study, we designed a multifunctional theranostic platform basing on magnetic-hydrogel (Fe3O4-OA-NIPAm-AA) nano-particles (MHNP) and a BC membrane for magnetic field treatment and PDT both in vitro and in vivo. We developed a laser-sensitive magnetic platform that repeatedly produces singlet oxygen (O-) and releases anticancer drugs doxorubicin (DOX) into the breast cancer cells when being irradiated by the 633 nm laser, which might consist of LMNs with DOX and hematoporphyrin monomethyl ether (HMME). In addition, folate acid (FA) as a target molecule can enhance the accumulation of nanocomposites to improve the eﬃciency of DOX and HMME. LMNs were absorbers of 633 nm laser irradiation and have served as photo-sensitizers for the oxidative damage of cancer cells. We encapsulated LMNs with BC membrane to prevent their rapid elimination from the tumor, which facilitated repeated dosing and PDT.
Doxorubicin hydrochloride (DOX) were purchased from Sun Yet-sen University Cancer Center, China. The HMME and N-Hydroxysuccinimidyl-4-azidobenzoate were purchased from Aladdin Industrial Inc., China, and folate acid (FA) were purchased from Xiang Bo Bio-Technology co., Ltd, China. All other chemicals in this study were analytical grade.
2.2. Synthesis of iron oxide magnetic nanoparticle
FeSO4·7H2O, FeCl3·6H2O, and NaOH were then dissolved in 30 mL of ultrapure water and placed in oil baths under nitrogen at 60 °C for 30 min, whereupon oleic acid (OA) and HCl were added at 70 °C for 3 h. Fe3O4 was packaged with oleic acid at 4 °C for 24 h. Anhydrous ethanol and deionized water were used to wash the three samples 3 times each. The nanoparticles were sorted by magnetic decantation and repeated with the deposit [29,36].
First synthesis of the MHNP. The as-prepared FA with highly active azido groups were immobilized on the surface of MHNP by irradiated with a UV lamp. Then, 3 mL 1 mg·ml−1 DOX and HMME PBS buﬀer solution was added to incubate with MHNP-FA for 72 h at 4 °C, allowing the suﬃcient adsorption of DOX and HMME. Furthermore, in order to remove unabsorbed drugs, the solution sorted by magnetic decantation and deionized water were used to wash the samples 3 times. Eventually, the LMNs drug was obtained. The details were referenced to our recent papers to synthesis of nanoparticles [29,36].