Browsing by Author "Li, Yulin"
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- Amphiphilic polymer-mediated formation of laponite-based nanohybrids with robust stability and pH sensitivity for anticancer drug deliveryPublication . Wang, Guoying; Maciel, Dina; Wu, Yilun; Rodrigues, João; Shi, Xiangyang; Yuan, Yuan; Liu, Changsheng; Tomás, Helena; Li, YulinThe development of pH-sensitive drug delivery nanosystems that present a low drug release at the physiological pH and are able to increase the extent of the release at a lower pH value (like those existent in the interstitial space of solid tumors (pH 6.5) and in the intracellular endolysosomal compartments (pH 5.0)) is very important for an efficient and safe cancer therapy. Laponite (LP) is a synthetic silicate nanoparticle with a nanodisk structure (25 nm in diameter and 0.92 nm in thickness) and negative-charged surface, which can be used for the encapsulation of doxorubicin (DOX, a cationic drug) through electrostatic interactions and exhibit good pH sensitivity in drug delivery. However, the colloidal instability of LP still limits its potential clinical applications. In this study, we demonstrate an elegant strategy to develop stable Laponite-based nanohybrids through the functionalization of its surface with an amphiphile PEG-PLA copolymer by a self-assembly process. The hydrophobic block of PEG-PLA acts as an anchor that binds to the surface of drug-loaded LP nanodisks, maintaining the core structure, whereas the hydrophilic PEG part serves as a protective stealth shell that improves the whole stability of the nanohybrids under physiological conditions. The resulting nanocarriers can effectively load the DOX drug (the encapsulation efficiency is 85%), and display a pH-enhanced drug release behavior in a sustained way. In vitro biological evaluation indicated that the DOX-loaded nanocarriers can be effectively internalized by CAL-72 cells (an osteosarcoma cell line), and exhibit a remarkable higher anticancer cytotoxicity than free DOX. The merits of Laponite/PEG-PLA nanohybrids, such as good cytocompatibility, excellent physiological stability, sustained pH-responsive release properties, and improved anticancer activity, make them a promising platform for the delivery of other therapeutic agents beyond DOX.
- An unusual morphology and crystallization behavior in in situ formed polyphenylene oxide/polyamide 6 blendsPublication . Li, Yulin; Yang, GuishengNovel polyphenylene oxide/polyamide 6 (PPO/ PA6) blends were synthesized via in situ polymerization of e-caprolactam with PPO dissolved in it. The introduction of 10 wt% PPO into PPO/PA6 led to phase inversion of the blends, which was nearly completed by incorporating 15 wt% PPO into the blends. A single crystallization temperature (Tc) of PA6 was detected for PPO/PA6 with 1–4 wt% PPO, while double Tc existed in the blends with 6–15 wt% PPO. After eliminating previous thermal his tory, PPO/PA6 containing no more than 6 wt% PPO gave a single melting point (Tm), but the blends with 10–15 wt% PPO exhibited double Tm. Increasing PPO content in PA6 resulted in the transformation of its crystal form from a-crystal to c-crystal, which might be attributed to hin drance of crystallization of PA6 particles in PPO-rich phase.
- Antitumor efficacy of doxorubicin encapsulated within PEGylated poly(amidoamine) dendrimersPublication . Liao, Huihui; Liu, Hui; Li, Yulin; Zhang, Mengen; Tomás, Helena; Shen, Mingwu; Shi, XiangyangWe report here a general approach to using poly(amidoamine) (PAMAM) dendrimers modified with polyethylene glycol (PEG) as a platform to encapsulate an anticancer drug doxorubicin (DOX) for in vitro cancer therapy applications. In this approach, PEGylated PAMAM dendrimers were synthesized by conjugating monomethoxypolyethylene glycol with carboxylic acid end group (mPEG-COOH) onto the surface of generation 5 amine-terminated PAMAM dendrimer (G5.NH2), followed by acetylation of the remaining dendrimer terminal amines. By varying the molar ratios of mPEG-COOH/G5.NH2, G5.NHAc-mPEGn (n55, 10, 20, and 40, respectively) with different PEGylation degrees were obtained. We show that the PEGylated dendrimers are able to encapsulate DOX with approximately similar loading capacity regardless of the PEGylation degree. The formed dendrimer/DOX complexes are water soluble and stable. In vitro release studies show that DOX complexed with the PEGylated dendrimers can be released in a sustained manner. Further cell viability assay in conjunction with cell morphology observation demonstrates that the G5.NHAc-mPEGn/DOX complexes display effective antitumor activity, and the DOX molecules encapsulated within complexes can be internalized into the cell nucleus, similar to the free DOX drug. Findings from this study suggest that PEGylated dendrimers may be used as a general drug carrier to encapsulate various hydrophobic drugs for different therapeutic applications.
- Antitumor efficacy of doxorubicin-loaded laponite/alginate hybrid hydrogelsPublication . Gonçalves, Mara; Figueira, Priscilla; Maciel, Dina; Rodrigues, João; Shi, Xiangyang; Tomás, Helena; Li, YulinDegradable hybrid hydrogels with improved stability are prepared by incorporating nanodisks of biocompatible laponite (LP) in alginate (AG) hydrogels using Ca2+ as a crosslinker. The Dox‐loaded hybrid hydrogels give a controlled Dox release at physiological environment in a sustained manner. Under conditions that mimic the tumor environment, both the sustainability in the Dox release (up to 17 d) and the release efficiency from LP/AG‐Dox hydrogels are improved. The in situ degradation of these hybrid hydrogels gives rise to nanohybrids that might serve as vehicles for carrying Dox through the cell membrane and diminish the effect of Dox ion‐trapping in the acidic extracellular environment of the tumor and/or in the endo‐lysosomal cell compartments.
- Biodegradable polymer nanogels for drug/nucleic acid deliveryPublication . Li, Yulin; Maciel, Dina; Rodrigues, João; Shi, Xiangyang; Tomás, Helena
- Dendrimer-assisted formation of fluorescent nanogels for drug delivery and intracellular imagingPublication . Gonçalves, Mara; Maciel, Dina; Capelo, Débora; Xiao, Shili; Sun, Wenjie; Shi, Xiangyang; Rodrigues, João; Tomás, Helena; Li, YulinAlthough, in general, nanogels present a good biocompatibility and are able to mimic biological tissues, their unstability and uncontrollable release properties still limit their biomedical applications. In this study, a simple approach was used to develop dual-cross-linked dendrimer/alginate nanogels (AG/G5), using CaCl2 as cross-linker and amine-terminated generation 5 dendrimer (G5) as a cocrosslinker, through an emulsion method. Via their strong electrostatic interactions with anionic AG, together with cross-linker Ca(2+), G5 dendrimers can be used to mediate the formation of more compact structural nanogels with smaller size (433 ± 17 nm) than that (873 ± 116 nm) of the Ca(2+)-cross-linked AG nanogels in the absence of G5. Under physiological (pH 7.4) and acidic (pH 5.5) conditions, the sizes of Ca(2+)-cross-linked AG nanogels gradually decrease probably because of their degradation, while dual-cross-linked AG/G5 nanogels maintain a relatively more stable structure. Furthermore, the AG/G5 nanogels effectively encapsulate the anticancer drug doxorubicin (Dox) with a loading capacity 3 times higher than that of AG nanogels. The AG/G5 nanogels were able to release Dox in a sustained way, avoiding the burst release observed for AG nanogels. In vitro studies show that the AG/G5-Dox NGs were effectively taken up by CAL-72 cells (a human osteosarcoma cell line) and maintain the anticancer cytotoxicity levels of free Dox. Interestingly, G5 labeled with a fluorescent marker can be integrated into the nanogels and be used to track the nanogels inside cells by fluorescence microscopy. These findings demonstrate that AG/G5 nanogels may serve as a general platform for therapeutic delivery and/or cell imaging.
- Development of bioabsorbable polylactide membrane with controllable hydrophilicity for adjustment of cell behavioursPublication . Yang, Yang; Qiu, Xiaofeng; Sun, Yi; Wang, Yifeng; Wang, Jine; Li, Yulin; Liu, ChangshengCell functions can be mediated through their interactions with the microenvironments, which highly depend on the surface state of the substrate. However, how to finely adjust the surface of biomaterials is still very challenging. In this study, poly(D,L-lactide) (PDLLA) with high molecular weight was synthesized via ring opening polymerization, which was hot-pressed into PDLLA membrane. In order to modify the hydrophobicity of the membrane (a limiting factor for its biomedical application), an amphiphilic monomethoxyl poly(ethylene glycol)-b-poly(D,L-lactide) (PEG-PDLLA) was selected to improve its surface hydrophilicity through a simple self-assembly approach. It was found that the contact angles of the modified membrane can be well controlled by variation of PEG-PDLLA concentrations. In vitro cell biological study indicates that optimized cell adhesion can be achieved on the modified membrane with a contact angle of around 50° via its self-assembly with an ethanol/water solution of PEG-PDLA (35 mg ml−1). The surface modification of the membrane also changed its biodegradation property in the process of its incubation period up to 240 days. The surface modification method may afford an effective way for adjustment of the surface (interface) of membrane (scaffolds) of different biomaterials, beyond polylactide.
- Injectable and biodegradable hydrogels: gelation, biodegradation and biomedical applicationsPublication . Li, Yulin; Rodrigues, João; Tomás, HelenaInjectable hydrogels with biodegradability have in situ formability which in vitro/in vivo allows an effective and homogeneous encapsulation of drugs/cells, and convenient in vivo surgical operation in a minimally invasive way, causing smaller scar size and less pain for patients. Therefore, they have found a variety of biomedical applications, such as drug delivery, cell encapsulation, and tissue engineering. This critical review systematically summarizes the recent progresses on biodegradable and injectable hydrogels fabricated from natural polymers (chitosan, hyaluronic acid, alginates, gelatin, heparin, chondroitin sulfate, etc.) and biodegradable synthetic polymers (polypeptides, polyesters, polyphosphazenes, etc.). The review includes the novel naturally based hydrogels with high potential for biomedical applications developed in the past five years which integrate the excellent biocompatibility of natural polymers/synthetic polypeptides with structural controllability via chemical modification. The gelation and biodegradation which are two key factors to affect the cell fate or drug delivery are highlighted. A brief outlook on the future of injectable and biodegradable hydrogels is also presented (326 references).
- Injectable hybrid laponite/alginate hydrogels for sustained release of methylene bluePublication . Li, Yulin; Santos, José Luís; Maciel, Dina; Tomás, Helena; Rodrigues, JoãoThe incorporation of biocompatible Laponite (LP) into alginate hydrogels greatly increases the drug encapsulation efficiency of methylene blue (MB). By raising the LP content from 0 to 0.5 wt.%, the half-release time (t1/2) of MB in oven-dried gels increases from ~2 h to ~10 h, while t1/2 in vacuum-dried gels slightly changes from ~1 h to ~2 h. Increasing LP content together with drying modes can induce the MB release mechanism froma diffusion-controlled release into a swelling-controlled one.
- Insight into the role of N,N-dimethylaminoethyl methacrylate (DMAEMA) conjugation onto poly(ethylenimine): cell viability and gene transfection studiesPublication . Nouri, Alireza; Castro, Rita; Kairys, Visvaldas; Santos, José L.; Rodrigues, João; Li, Yulin; Tomás, HelenaIn the present study, the effect of N,N-dimethylaminoethyl methacrylate (DMAEMA) conjugation onto branched poly(ethylenimine) (PEI) with different grafting degree was examined for gene delivery applications. The DMAEMA-grafted-PEI conjugates were characterized and complexed with plasmid DNA (pDNA) at various concentrations, and the physicochemical properties, cell viability, and in vitro transfection efficiency of the complexes were evaluated in HEK 293T cells. Computational techniques were used to analyze the interaction energies and possible binding modes between DNA and conjugates at different grafting degrees. The cytotoxicity analysis and in vitro transfection efficiency of the conjugate/pDNA complexes exhibited a beneficial effect of DMAEMA conjugation when compared to PEI alone. The computational results revealed that the DNA/vector interaction energy decreases with increasing grafting degree, which can be associated to an enhanced release of the pDNA from the carrier once inside cells. The results indicate the significance of DMAEMA conjugation onto PEI as a promising approach for gene delivery applications.