Synthesis of PEGylated cationic curdlan derivatives with enhanced biocompatibility

Muqier, Muqier; Xiao, Hai; Yu, Xiang; Li, Yifeng; Bao, Mingming; Bao, Qingming; Han, Shuqin; Baigude, Huricha

doi:10.1080/09205063.2021.1992589

Cited by 6 publications

(4 citation statements)

References 40 publications

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“…In our previous study, we discovered that by targeting cell surface adenosine receptors such as A 2B R with AMP ligand-functionalized Curdlan nanoparticles (CuAMP4), tumor cell-specific siRNA can be achieved . Meanwhile, PEGylation of cationic polymers can significantly reduce the cytotoxicity and improve the nucleic acid delivery efficiency of the polymeric nanoparticle . In order to develop a siRNA drug carrier that is extremely biocompatible and targets cancer cells as well as TAMs, we initially linked PEG with cleavable disulfide to the structure of CuAMP4.…”

Section: Resultsmentioning

confidence: 99%

“…23 Nevertheless, the development of an optimal nanocarrier for the simultaneous delivery of CpG and siSTAT3 to both tumor cells and TAMs is necessary. By sequentially conjugating AMP and mannose to a PEGylated Curdlan derivative, 19 we obtained the dual-ligand-functionalized CuAMP polymer, which not only had lower cytotoxicity compared to the parental polymer but also enhanced siRNA delivery to the cancer line in vitro (Figure 2D−F). Significantly, the internalization of siRNA-loaded CuMAN nanoparticles by AR-expressing cancer cells was inhibited by the natural ligand of AR (e.g., free AMP) (Figure 3C).…”

Section: ■ Discussionmentioning

confidence: 99%

“…16a Meanwhile, PEGylation of cationic polymers can significantly reduce the cytotoxicity and improve the nucleic acid delivery efficiency of the polymeric nanoparticle. 19 In order to develop a siRNA drug carrier that is extremely biocompatible and targets cancer cells as well as TAMs, we initially linked PEG with cleavable disulfide to the structure of CuAMP4. This was achieved by utilizing an EDC reagent in an MES buffer (denoted the resulting polymer by pAVC).…”

Section: Synthesis and Characterization Of Cuman Polymersmentioning

confidence: 99%

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Tumor-Targeted Codelivery of CpG and siRNA by a Dual-Ligand-Functionalized Curdlan Nanoparticle

Bao,

Xiao

et al. 2024

Biomacromolecules

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The simultaneous delivery of CpG oligonucleotide along with short interfering RNA (siRNA) has the potential to significantly boost the anticancer impact of siRNA medications. Our previous research demonstrated that Curdlan nanoparticles functionalized with adenosine are capable of selectively delivering therapeutic siRNA to cancerous cells through endocytosis mediated by adenosine receptors. Herein, we synthesized a dual-ligand-functionalized Curdlan polymer (denoted by CuMAN) to simultaneously target tumor cells and tumor-associated macrophages (TAMs). CuMAN nanoparticles containing CpG and siRNA demonstrated enhanced uptake by B16F10 tumor cells and bone marrow-derived macrophages, which are facilitated by AR on tumor cells and mannose receptor on macrophages. This led to increased release of pro-inflammatory cytokines in both in vitro and in vivo settings. The synergistic effect of CpG on TAMs and RNAi on tumor cells mediated by the CuMAN nanoparticle not only suppressed the tumor growth but also strongly inhibited the lung metastasis. Our findings indicate that the CuMAN nanoparticle has potential as an effective dual-targeting delivery system for nucleic acid therapeutics.

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Section: Resultsmentioning

confidence: 99%

Section: ■ Discussionmentioning

confidence: 99%

Section: Synthesis and Characterization Of Cuman Polymersmentioning

confidence: 99%

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Tumor-Targeted Codelivery of CpG and siRNA by a Dual-Ligand-Functionalized Curdlan Nanoparticle

Bao,

Xiao

et al. 2024

Biomacromolecules

Self Cite

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“…As shown in Figure 3(A) and (B) , the cytotoxicity of PEGylated peptides (PEG 12 LA and PEG 24 LA) were significantly lower than the non-PEGylated LA peptide at high concentrations (50 and 25 μg/mL), indicating PEGylation could decrease the vector’s cytotoxicity in vitro . The better biocompatibility of these PEGylated peptide vectors might be due to the PEG chain’s partially charge shielding effect of the high positive charges of LA peptide, as high positive charge vectors have been reported to produce strong interaction with the negatively charged cell membranes and endosomal membranes to cause cells death (Muqier et al., 2022 ). Similarly, the cytotoxicity of PEGylated peptides/mRNA nano self-assemblies was significantly lowered at all test w/w ratios ( Figure 3C–D ).…”

Section: Resultsmentioning

confidence: 99%

PEGylated pH-responsive peptide-mRNA nano self-assemblies enhance the pulmonary delivery efficiency and safety of aerosolized mRNA

Zheng

Ding

et al. 2023

Drug Delivery

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Inhalable messenger RNA (mRNA) has demonstrated great potential in therapy and vaccine development to confront various lung diseases. However, few gene vectors could overcome the airway mucus and intracellular barriers for successful pulmonary mRNA delivery. Apart from the low pulmonary gene delivery efficiency, nonnegligible toxicity is another common problem that impedes the clinical application of many non-viral vectors. PEGylated cationic peptide-based mRNA delivery vector is a prospective approach to enhance the pulmonary delivery efficacy and safety of aerosolized mRNA by oral inhalation administration. In this study, different lengths of hydrophilic PEG chains were covalently linked to an amphiphilic, water-soluble pH-responsive peptide, and the peptide/mRNA nano self-assemblies were characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The in vitro mRNA binding and release, cellular uptake, transfection, and cytotoxicity were studied, and finally, a proper PEGylated peptide with enhanced pulmonary mRNA delivery efficiency and improved safety in mice was identified. These results showed that a proper N-terminus PEGylation strategy using 12-monomer linear monodisperse PEG could significantly improve the mRNA transfection efficiency and biocompatibility of the non-PEGylated cationic peptide carrier, while a longer PEG chain modification adversely decreased the cellular uptake and transfection on A549 and HepG2 cells, emphasizing the importance of a proper PEG chain length selection. Moreover, the optimized PEGylated peptide showed a significantly enhanced mRNA pulmonary delivery efficiency and ameliorated safety profiles over the non-PEGylated peptide and Lipofectamine TM 2000 in mice. Our results reveal that the PEGylated peptide could be a promising mRNA delivery vector candidate for inhaled mRNA vaccines and therapeutic applications for the prevention and treatment of different respiratory diseases in the future.

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Dual-modified starch micelles as nanocarriers for efficient encapsulation and controlled release of walnut-derived active peptides

Wang,

Qi,

Hou

et al. 2024

Food Chemistry

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Synthesis of PEGylated cationic curdlan derivatives with enhanced biocompatibility

Cited by 6 publications

References 40 publications

Tumor-Targeted Codelivery of CpG and siRNA by a Dual-Ligand-Functionalized Curdlan Nanoparticle

Tumor-Targeted Codelivery of CpG and siRNA by a Dual-Ligand-Functionalized Curdlan Nanoparticle

PEGylated pH-responsive peptide-mRNA nano self-assemblies enhance the pulmonary delivery efficiency and safety of aerosolized mRNA

Dual-modified starch micelles as nanocarriers for efficient encapsulation and controlled release of walnut-derived active peptides

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