ABSTRACT
Precisely delivering combinational therapeutic agents has become a crucial challenge for anti-tumor treatment. In this study, a novel redox-responsive polymeric prodrug (molecular weight, MW: 93.5 kDa) was produced by reversible addition-fragmentation chain transfer (RAFT) polymerization. The amphiphilic block polymer-doxorubicin (DOX) prodrug was employed to deliver a hydrophobic photosensitizer (PS), chlorin e6 (Ce6), and the as-prepared nanoscale system [NPs(Ce6)] was investigated as a chemo-photodynamic anti-cancer agent. The glutathione (GSH)-cleavable disulfide bond was inserted into the backbone of the polymer for biodegradation inside tumor cells, and DOX conjugated onto the polymer with a disulfide bond was successfully released intracellularly. NPs(Ce6) released DOX and Ce6 with their original molecular structures and degraded into segments with low MWs of 41.2 kDa in the presence of GSH. NPs(Ce6) showed a chemo-photodynamic therapeutic effect to kill 4T1 murine breast cancer cells, which was confirmed from a collapsed cell morphology, a lifted level in the intracellular reactive oxygen species, a reduced viability and induced apoptosis. Moreover, ex vivo fluorescence images indicated that NPs(Ce6) retained in the tumor, and exhibited a remarkable in vivo anticancer efficacy. The combinational therapy showed a significantly increased tumor growth inhibition (TGI, 58.53%). Therefore, the redox-responsive, amphiphilic block polymeric prodrug could have a great potential as a chemo-photodynamic anti-cancer agent.
ABSTRACT
Multi-modal therapeutics are emerging for simultaneous diagnosis and treatment of cancer. Polymeric carriers are often employed for loading multiple drugs due to their versatility and controlled release of these drugs in response to a tumor specific microenvironment. A theranostic nanomedicine was designed and prepared by complexing a small gadolinium chelate, conjugating a chemotherapeutic drug PTX through a cathepsin B-responsive linker and covalently bonding a fluorescent probe pheophorbide a (Ppa) with a branched glycopolymer. The branched prodrug-based nanosystem was degradable in the tumor microenvironment with overexpressed cathepsin B, and PTX was simultaneously released to exert its therapeutic effect. The theranostic nanomedicine, branched glycopolymer-PTX-DOTA-Gd, had an extended circulation time, enhanced accumulation in tumors, and excellent biocompatibility with significantly reduced gadolinium ion (Gd
ABSTRACT
BACKGROUND: Recently biodegradable hydrogel has been extensively used to delivery anticancer drug and bioactive macromolecule. However, to protect the activity of the bioactive macromolecule, we need to obtain series of hydrogel which have milder hydrogelation conditions and shorter hydroglation time.OBJECTIVE: To prepare enantiomeric poly(L-Lactic acid) (PLLA)-poly(ethylene glycol (PEG)-PLLA/ poly(D-Lactic acid) (PDLA)-PEG-PDLA stereocomplex hydrogel which has shorter hydroglation time, to physically encapsulate a model drug-lysozyme and sustained release it from the hydrogel. METHODS: Triblock copolymers of PLLA-PEG-PLLA and PDLA-PEG-PDLA were synthesized by ring-opening polymerization of L(D)-lactide using PEG as the initiator and Sn(Oct)2 as the catalyst. The triblock copolymers were characterized by 1H nuclear magnetic resonance, FT-IR and X-Ray diffractometry. A hydrogel was prepared from an aqueous mixture of PLLA20-PEG227-PLLA20 and PDLA21-PEG227-PDLA21 (10 wt% concentration) at room temperature for 12 hours. X-Ray diffractometry test was used to research the gelation mechanism. The release profile of the lysozyme as a model drug from the hydrogel was tested. The morphology of the freeze-dried hydrogel was investigated by scanning electron microscope. The cytotoxicity of the hydrogel was evaluated by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide) assay.RESULTS AND CONCLUSION: Triblock copolymers of PLLA-PEG-PLLA and PDLA-PEG-PDLA were obtained. Both the PEG and PLA blocks in the copolymers could crystallize, but the crystallization of the PEG block was predominant. The stereocomplex formation between the PLLA and PDLA blocks within the hydrogel was confirmed by the X-Ray diffractometry analysis. The release profile of the lysozyme from the hydrogel exhibited a sustained-release pattern with a duration period of 7 days. The hydrogel exhibited a 3D interconnected porous structure with 50-100 μm pore size after being freeze-dried. The mouse fibroblast cell viability percentage was 99.3% after the cells contacted with the 100% extracted liquid for 72 hours.
ABSTRACT
9-nitro camptothecin (9-NC) loaded amphiphilic copolymer micelles were prepared with solvent evaporation method. The effects of temperature, distilled water volume, stirring rate, and drug input amount on the size and drug content of micelles were further discussed. As a result, well dispersed spherical micelles with drug content of 4.9 percent and 50 -70 nanometers in diameter were achieved with the following preparation conditions: water bath temperature 60 degrees C , distilled water amount 16 ml, stirring rate 6 500 r/min, and drug input amount 1.2 mg. 9-NC release profiles in vitro illustrated that drug release from micelles included initial burst release and following controlled release. The release rate was decreased with the increase of drug content.
Subject(s)
Humans , Antineoplastic Agents , Chemistry , Camptothecin , Chemistry , Delayed-Action Preparations , Chemistry , Drug Carriers , Chemistry , Drug Compounding , Micelles , Nanoparticles , Particle Size , Polymers , SolubilityABSTRACT
Using the CT data, we have constructed the finite element models of human femur distally amputated at high-position, middle-position and low-position, along with distally osseointegrated implant under the maximal load during a normal walking cycle. Results of finite element analysis revealed: the maximal stress of implant is produced near the exit of the amputated limb, where the fatigue breakpoint caused by cyclic stress would take place. With the ascending of truncated position, the peri-implant interfacial stress of bone increases. There is severe stress-shielding at the bone-implant interface, and there is concentration of stress at the end of implant and at the 3/4 point of femur, which would lead to bone loss and bone resorption and would shorten the longevity of implant. The results also showed that the curvature of natural bone has notable effect on the stress distribution, which should not be neglected. These data may provide reliable reference for the design and research of osseointegarted artificial limb.