Xinru You

Polymeric nanoparticles for colon cancer therapy: overview and perspectives

Colorectal cancer (CRC) is the third-most common malignant tumour and is associated with high morbidity and mortality worldwide. This review summarizes the recent progress in the development of polymeric nanoparticle systems for colon cancer therapy.

TPGS modified reduced bovine serum albumin nanoparticles as a lipophilic anticancer drug carrier for overcoming multidrug resistance

In this study, a novel protein-polymer conjugate, d-α-tocopheryl polyethylene glycol succinate modified reduced bovine serum albumin (TPGS-Re-BSA, TRB), was synthesized for lipophilic anticancer drug delivery, and its unique ability to overcome drug resistance was explored. This conjugate was extensively characterized for its chemical structure, average molecular weight, secondary structure, degree of substitution, hydrophobicity, particle size and zeta potential. PTX-loaded nanoparticles (NPs) with diameters of 170-370 nm and drug loading efficiency of up to 13.62% were successfully prepared by the dialysis method. These drug-loaded NPs were found to exhibit a sustained release of PTX at pH 7.4, 6.5 and 5.5. Moreover, great anti-tumor activity in drug sensitive MCF-7 cells was observed in the in vitro anti-tumor studies. In particular, enhanced cytotoxicity and PTX-induced apoptosis were observed in the drug-resistant MCF-7/ADR cells compared to the Taxol and PTX-loaded BSA NPs. This could be attributed to the significant inhibition of P-gp activity and reduced ATP levels due to the presence of TRB NPs. Lastly, in vivo tumor inhibition assay verified the higher efficacy of TRB NPs. Overall, the results suggest that this TRB NPs could provide an effective carrier system for the delivery of anticancer agents.

Development of a reactive oxygen species (ROS)-responsive nanoplatform for targeted oral cancer therapy

In this study, for effective oral cancer therapy, a new targeted and ROS-triggered drug delivery nanoplatform was developed from the RGD-PEG-TK-PLGA polymer, in which the ROS-responsive TK containing linker was connected with PEG and PLGA. RGD in the drug delivery system (DDS) presented here was used to target cancer cells. This new nanoplatform shows high stability, good targeting ability, excellent ROS sensitivity and excellent biocompatibility. Loaded with DOX and alpha-TOS, the formulated nanoparticles (NPs) demonstrate much better cellular uptake efficiency and higher inhibition performance towards the oral tongue Cal27 cancer cell line. In vivo anticancer evaluation indicates that DOX and alpha-TOS loaded RGD-PEG-TK-PLGA NPs have no toxicity to mice and showed significantly improved therapeutic efficacy against tumors. Therefore, this polymeric NP platform presents great potential as a new DDS for oral cancer chemotherapy.

Development of graphene oxide-wrapped gold nanorods as robust nanoplatform for ultrafast near-infrared SERS bioimaging

The rapid development of near-infrared surface-enhanced Raman scattering (NIR SERS) imaging technology has attracted strong interest from scientists and clinicians due to its narrow spectral bandwidth, low background interference, and deep imaging depth. In this report, the graphene oxide (GO)-wrapped gold nanorods (GO@GNRs) were developed as a smart and robust nanoplatform for ultrafast NIR SERS bioimaging. The fabricated GO@ GNRs could efficiently load various NIR probes, and the in vitro evaluation indicated that the nanoplatform could exhibit a higher NIR SERS activity in comparison with traditional gold nanostructures. The GOs were prepared by directly pyrolyzing citric acid for greater convenience, and GO@GNRs were fabricated via a facile synthesis strategy. Higher NIR SERS activity, facile synthesis method, excellent biocompatibility, and superb stability make the GO@GNRs/probe complex promising nanoprobes for NIR SERS-based bioimaging applications.

Hybrid hydrogels with high strength and biocompatibility for bone regeneration

The development of hydrogels for bone regeneration has highlighted the challenge that load-bearing hydrogels need to be biocompatible while achieving high strength. Several approaches have been reported to improve the toughness of hydrogels, but achieving high toughness and biocompatibility simultaneously remains a challenge. Here we report a polyacrylic acid/alginate/demineralized bone matrix (PAA/Alg/DBM) hybrid double network hydrogel, which was synthesized by a two-step sequential polymerization with embedded DBM, possessing both high strength and biocompatibility. With the persistence of DBM, it can promote the synthesis of VEGF and bFGF and the ALP activity of MG63 cells on hydrogel. All the results suggest that this hybrid double network hydrogel have potential for future application in bone regeneration.

BAPTA-AM Nanoparticle for the Curing of Acute Kidney Injury Induced by Ischemia/Reperfusion

Ischemia-reperfusion (I/R) is a major cause of acute kidney injury (AKI), which is associated with unacceptably high mortality rates in ICU. This research was designed to explore the therapeutic effect of BAPTA-AM (1,2-Bis(2-aminophenoxy) ethane-N,N,N,N-tetraacetic acid tetrakis(acetoxymethyl ester)) nanoparticle (BA-N) on AKI. BA-N was developed by liposome strategy and characterized by standard methods. The rat model was selected and the rats were randomly allocated into four groups: (1) Normal group; (2) Sham-operated group; (3) Model group (I/R + NS); (4) BA-N treatment group (I/R + BA-N). AKI model was established via clipping the bilateral renal artery with a microvascular clamp for 45 min. After reperfusion, serum cystatin C (Cys C), creatinine (Cr), blood urea nitrogen (BUN), lactate dehydrogenase (LDH) and caspase 3 levels were determined for the assessment of renal function. Kidney samples were then collected for the measurement of renal malondialdehyde (MDA) level and superoxide dismutase (SOD) activity. The assays of histological examination, ELISA, immunohistochemistry, western blot, TUNEL and RT-PCR were utilized for the detection of apoptosis. The results demonstrated that AKI model caused a significant decreasing in SOD activity, accompanied by a remarkable increase in Cys C, Cr, BUN, LDH, MDA, caspase 3 and cytochrome c (Cyt C) level, compared to the control group. BA-N (100 μg/kg i.v.) significantly improved renal function and histopathological appearance, restored MDA level and SOD activity, decreased Bax/Bcl-2 ratio, caspase 3 activity, Cyt C release and TUNEL positive apoptotic cells. Our studies indicated that BA-N plays a renal-protective role, probably through antiapoptotic and antioxidant mechanisms. BA-N may regulate mitochondria pathway via decreasing Bax/Bcl-2 ratio, inhibiting caspase 3 expression and Cyt C release. Overall, BA-N may have potentials as an anti-AKI drug.

Arginine-based poly(ester amide) nanoparticle platform: From structure–property relationship to nucleic acid delivery

Many different types of polycations have been vigorously studied for nucleic acid delivery, but a systematical investigation of the structure-property relationships of polycations for nucleic acid delivery is still lacking. In this study, a new library of biodegradable and biocompatible arginine-based poly(ester amide) (Arg-PEA) biomaterials was designed and synthesized with a tunable structure for such a comprehensive structure-property research. Nanoparticle (NP) complexes were formed through the electrostatic interactions between the polycationic Arg-PEAs and anionic nucleic acids. The following structure effects of the Arg-PEAs on the transfection efficiency of nucleic acids were investigated: 1) the linker/spacer length (length effect and odd-even effect); 2) salt type of arginine; 3) the side chain; 4) chain stiffness; 5) molecular weight (MW). The data obtained revealed that a slight change in the Arg-PEA structure could finely tune its physicochemical property such as hydrophobicity, and this could subsequently affect the nanoparticle size and zeta potential, which, in turn, regulate the transfection efficiency and silencing outcomes. A further study of the Arg-PEA/CpG oligodeoxynucleotide NP complexes indicated that the polymer structure could precisily regulate the immune response of CpG, thus providing a new potential nano-immunotherapy strategy. The in vitro data have further confirmed that the Arg-PEA NPs showed a satisfactory delivery performance for a variety of nucleic acids. Therefore, the data from the current study provide comprehensive information about the Arg-PEA structure-transfection property relationship; the tunable property of the library of Arg-PEA biomaterials can be one of the promising candidates for nucleic acid delivery and other biomedical applications. STATEMENT OF SIGNIFICANCE Polycations have being intensive utilized for nucleic acid delivery. However, there has not been elucidated about the relationship between polycations structure and the physicochemical properties/biological function. In this timely report, an arginine based poly(ester amide) (Arg-PEA) library was prepared with finely tunable structure to systematically investigate the structure-property relationships of polycations for nucleic acid delivery. The results revealed that slight change of Arg-PEA structure could finely tune the physicochemical property (such as hydrophobicity), which subsequently affect the size and zeta potential of Arg-PEA/nucleic acid nanoparticles(NPs), and finally regulate the resulting transfection or silencing outcomes. Further study of Arg-PEA/CpG NPs indicated that the polymer structure could precisely regulate immuno response of CpG, providing new potential nano-immunotherapy strategy. In vitro evaluations confirmed that the NPs showed satisfied delivery performance for a variety types of nucleic acids. Therefore, these studies provide comprehensive information of Arg-PEA structure-property relationship, and the tunable properties of Arg-PEAs make them promising candidates for nucleic acid delivery and other biomedical applications. Overall, we have shown enough significance and novelty in terms of nucleic acid delivery, biomaterials, pharmaceutical science and nanomedicine.

Evaluation of tofu as a potential tissue engineering scaffold

Tofu not only is a delicious vegetarian food, but also shows potential biomedical applications for its high protein content and typical porous scaffold structure. Herein, two kinds of porous soybean scaffolds were developed, the first based on the traditional tofu manufacturing processes, the second modified via covalent crosslinking. The morphology, physicochemical properties and biocompatibility in vitro and in vivo were systematically investigated. A similar porous micromorphology was observed in both the tofu scaffolds and crosslinked soybean protein scaffolds. Both scaffolds exhibited good cell proliferation and cellular adherence. No obvious inflammatory response was observed after subcutaneous implantation tests for either material. These results demonstrated that the tofu scaffolds or soybean protein scaffolds fabricated by tofu processing have potential as new food-source biomaterials in tissue engineering applications.

Human albumin fragments nanoparticles as PTX carrier for improved anti-cancer efficacy

For enhanced anti-cancer performance, human serum albumin fragments (HSAFs) nanoparticles (NPs) were developed as paclitaxel (PTX) carrier in this paper. Human albumins were broken into fragments via degradation and crosslinked by genipin to form HSAF NPs for better biocompatibility, improved PTX drug loading and sustained drug release. Compared with crosslinked human serum albumin NPs, the HSAF-NPs showed relative smaller particle size, higher drug loading, and improved sustained release. Cellular and animal results both indicated that the PTX encapsulated HSAF-NPs have shown good anti-cancer performance. And the anticancer results confirmed that NPs with fast cellular internalization showed better tumor inhibition. These findings will not only provide a safe and robust drug delivery NP platform for cancer therapy, but also offer fundamental information for the optimal design of albumin based NPs.