scholarly journals Polyethylenimine-Based Theranostic Nanoplatform for Glioma-Targeting SPECT Imaging and Anticancer Drug Delivery

2020 ◽  
Author(s):  
Lingzhou Zhao ◽  
Jingyi Zhu ◽  
Jiali Gong ◽  
Ningning Song ◽  
Shan Wu ◽  
...  

Abstract Background Glioma is the deadliest brain cancer in adults because the blood-brain-barrier (BBB) prevents the vast majority of therapeutic drugs from entering into the central nervous system. The development of BBB-penetrating drug delivery systems for glioma therapy still remains a great challenge. In this study, we aimed to design and develop a theranostic nanocomplex with enhanced BBB penetrability and tumor-targeting efficiency for glioma (SPECT) imaging and anticancer drug delivery. Results This multifunctional nanocomplex was manufactured using branched polyethylenimine (PEI) as a template to sequentially conjugate with methoxypolyethylene glycol ( m PEG), glioma-targeting peptide chlorotoxin (CTX), and diethylenetriaminepentaacetic acid (DTPA) for 99m Tc radiolabeling on the surface of PEI. After the acetylation of the remaining PEI surface amines using acetic anhydride (Ac 2 O), the CTX-modified PEI ( m PEI-CTX) was utilized as a carrier to load chemotherapeutic drug doxorubicin (DOX) in its interior cavity. The m PEI-CTX/DOX complex had excellent water dispersibility and released DOX in a sustainable and pH-dependent manner; furthermore, it showed targeting specificity and therapeutic effect of DOX toward glioma cells in vitro and in vivo (a subcutaneous tumor mouse model). Owing to the unique biological properties of CTX, the m PEI-CTX/DOX complex was able to cross the BBB and accumulate at the tumor site in an orthotopic rat glioma model. In addition, after efficient radiolabeling of PEI with 99m Tc via DTPA, the 99m Tc-labeled complex could help to visualize the drug accumulation in tumors of glioma-bearing mice and the drug delivery into the brains of rats through SPECT imaging. Conclusions These results indicate the potential of the developed PEI-based nanocomplex in facilitating glioma-targeting SPECT imaging and chemotherapy.

2019 ◽  
Vol 11 (42) ◽  
pp. 39395-39395
Author(s):  
Gargi Mishra ◽  
Souryadeep Bhattacharyya ◽  
Vipul Bhatia ◽  
Bushra Ateeq ◽  
Ashutosh Sharma ◽  
...  

2017 ◽  
Vol 9 (40) ◽  
pp. 34625-34633 ◽  
Author(s):  
Gargi Mishra ◽  
Souryadeep Bhattacharyya ◽  
Vipul Bhatia ◽  
Bushra Ateeq ◽  
Ashutosh Sharma ◽  
...  

2020 ◽  
Author(s):  
AL-DYBIAT Iman ◽  
BAITUKHA Alibi ◽  
PIMPIE Cynthia ◽  
KACI Rachid ◽  
POCARD Marc ◽  
...  

Abstract Background: It may be impossible to perform cancer surgery with free margins in the presence of an unresectable structure. Local drug treatment after surgery has been proposed to increase the rate of tumor control. Methods: Multi-nanolayers (10-330nm) were generated by a low-pressure (375mTorr) inductively coupled plasma (13.56MHz) reactor for anticancer drug delivery by the deposition of polycaprolactone-polyethylene glycol multistack barrier on the collagen membrane (100µm thickness). Carboplatin (300µg/cm 2 ) was used for the in vitro and in vivo investigations. Energy-dispersive X-ray spectroscopy (15keV), scanning electron microscopy and inductively coupled plasma mass spectrometry were used to detect the presence of carboplatin in the nanolayer, the tumor sample and the culture medium. Preclinical studies were performed on ovarian (OVCAR-3NIH) and colon (CT26) cancer cell lines as xenografts (45 days) and allografts (23 days) in Swiss-nude (n=6) and immunocompetent BALB/cByJ mice (n=24), respectively. Results: The loading of carboplatin or other drugs between the nanofilm on the collagen membrane did not modify the mesh complex architecture or the drug properties. Drugs were detectable on the membrane for more than two weeks in the in vitro analysis and more than 10 days in the in vivo analysis. Cytotoxic mesh decreased cell adherence (down 5.42-fold) and induced cancer cell destruction (up to 7.87-fold). Implantation of the mesh on the mouse tumor nodule modified the cell architecture and decreased the tumor size (50.26%) compared to the control by inducing cell apoptosis. Conclusion: Plasma technology allows a mesh to be built with multi-nanolayer anticancer drug delivery on collagen membranes.


2021 ◽  
Vol 20 ◽  
pp. 153303382110278
Author(s):  
Yayan Yang ◽  
Qian Feng ◽  
Chuanfeng Ding ◽  
Wei Kang ◽  
Xiufeng Xiao ◽  
...  

Although Epirubicin (EPI) is a commonly used anthracycline for the treatment of breast cancer in clinic, the serious side effects limit its long-term administration including myelosuppression and cardiomyopathy. Nanomedicines have been widely utilized as drug delivery vehicles to achieve precise targeting of breast cancer cells. Herein, we prepared a DSPE-PEG nanocarrier conjugated a peptide, which targeted the breast cancer overexpression protein Na+/K+ ATPase α1 (NKA-α1). The nanocarrier encapsulated the EPI and grafted with the NKA-α1 targeting peptide through the click reaction between maleimide and thiol groups. The EPI was slowly released from the nanocarrier after entering the breast cancer cells with the guidance of the targeting NKA-α1 peptide. The precise and controllable delivery and release of the EPI into the breast cancer cells dramatically inhibited the cells proliferation and migration in vitro and suppressed the tumor volume in vivo. These results demonstrate significant prospects for this nanocarrier as a promising platform for numerous chemotherapy drugs.


2019 ◽  
Vol 30 ◽  
pp. v191
Author(s):  
Y. Yen ◽  
L. Yu ◽  
H. Qian ◽  
L. Wang ◽  
B. Liu ◽  
...  

2000 ◽  
Vol 68 (7) ◽  
pp. 4064-4074 ◽  
Author(s):  
Isabelle Batisson ◽  
Maurice Der Vartanian ◽  
Brigitte Gaillard-Martinie ◽  
Michel Contrepois

ABSTRACT We have successfully used the major subunit ClpG ofEscherichia coli CS31A fimbriae as an antigenic and immunogenic exposure-delivery vector for various heterologous peptides varying in nature and length. However, the ability of ClpG as a carrier to maintain in vitro and in vivo the native biological properties of passenger peptide has not yet been reported. To address this possibility, we genetically fused peptides containing all or part of the E. coli human heat-stable enterotoxin (STh) sequence to the amino or carboxyl ends of ClpG. Using antibodies to the ClpG and STh portions for detecting the hybrids; AMS (4-acetamido-4′-maleimidylstilbene-2,2′-disulfonate), a potent free thiol-trapping reagent, for determining the redox state of STh in the fusion; and the suckling mouse assay for enterotoxicity, we demonstrated that all ClpG-STh proteins were secreted in vitro and in vivo outside the E. coli cells in a heat-stable active oxidized (disulfide-bonded) form. Indeed, in contrast to many earlier studies, blocking the natural NH2 or COOH extremities of STh had, in all cases, no drastic effect on cell release and toxin activity. Only antigenicity of STh C-terminally extended with ClpG was strongly affected in a conformation-dependent manner. These results suggest that the STh activity was not altered by the chimeric structure, and therefore that, like the natural toxin, STh in the fusion had a spatial structure flexible enough to be compatible with secretion and enterotoxicity (folding and STh receptor recognition). Our study also indicates that disulfide bonds were essential for enterotoxicity but not for release, that spontaneous oxidation by molecular oxygen occurred in vitro in the medium, and that the E. coli cell-bound toxin activity in vivo resulted from an effective export processing of hybrids and not cell lysis. None of the ClpG-STh subunits formed hybrid CS31A-STh fimbriae at the cell surface ofE. coli, and a strong decrease in the toxin activity was observed in the absence of CS31A helper proteins. In fact, chimeras translocated across the outer membrane as a free folded monomer once they were guided into the periplasm by the ClpG leader peptide through the CS31A-dependent secretory pathway. In summary, ClpG appears highly attractive as a carrier reporter protein for basic and applied research through the engineering of E. coli for culture supernatant delivery of an active cysteine-containing protein, such as the heat-stable enterotoxin.


RSC Advances ◽  
2015 ◽  
Vol 5 (50) ◽  
pp. 40103-40110 ◽  
Author(s):  
Qiang Wu ◽  
Ruifang Li ◽  
Chao Zhao ◽  
Jiejie Ren ◽  
Keyuan Du ◽  
...  

MSNs-HP loaded with only a low amount of a drug (DOX0.3) achieve a similar antitumor efficacy to that of large doses of the drug (DOX2.0, 7-fold higher in dosage than DOX0.3).


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