One-step Self-assembly/polymerization Fabrication and Biomedical Application of Carboplatin@Dextran Nanocarrier†

doi:10.7503/cjcu20180860

Abstract

Abstract:

We introduced disulfide bond in the crosslinking points of the carboplatin@dextran to endow the reducing environmental sensitivity to the nanocarriers. Its structure, particle size and morphology of the nanocarrier were characterized by means of dynamic light scattering(DLS), ¹H NMR and FTIR. The results showed that the size of the nanocarrier was (92±0.2) nm. In vitro drug release studies disclosed that the carboplatin inside the nanocarrier can be released for 80% in 72 h in a reducing environment. The cell uptake experiments showed that the nanocarriers loaded with carboplatin could efficiently enter the cell nuclei within 4 h. The half maximal inhibitory concentration(IC₅₀) of the carboplatin@dextran nanocarrier was 25.32 μg/mL, which had similar cytotoxicity to the free carboplatin at the same concentration. The above results demonstrate that carboplatin@dextran nanocarrier prepared by the one-step method has a good biomedical application prospect.

Key words: One-stepfabrication, Graft polymerization assisted self-assembly, Carboplatin@dextran nanocarrier, Reducing environmental responsivity

CLC Number:

O636.1

TrendMD:

GAO Miaomiao,WANG Chenglong,DOU Hongjing,XU Guoxiong. One-step Self-assembly/polymerization Fabrication and Biomedical Application of Carboplatin@Dextran Nanocarrier^†[J]. Chem. J. Chinese Universities, 2019, 40(6): 1301.

Figures/Tables 10

Scheme 1 Schematic illustration depicting the fabrication of the DAPt and their tumor-microenvironment sensitive drug release behavior

Fig.1 1H NMR(A) and FTIR(B) spectra of Dextran(a), D2A2(b) and D2A2Pt80(c)

Scheme 2 Molecular structure of DAPt

Table 1 Characteristics of DAPt

Sample	n_Glu∶n_Monoter	m_Dextran∶m_CBP	Size/nm	PDI	EE(%)	LC(%)
D2A1Pt160	1∶0.5	80∶1	73±0.7	0.34	11.59	0.15
D2A2Pt160	1∶1	80∶1	88±0.6	0.23	13.14	0.15
D2A3Pt160	1∶1.5	80∶1	105±0.6	0.31	23.42	0.27
D2A2Pt80	1∶1	40∶1	92±0.2	0.23	29.18	0.63

Fig.2 TEM image(A) and DLS(B) of D2A2Pt80

Fig.3 Drug release curves of D2A2Pt80 in different conditions a. pH=7.4 PBS; b. pH=7.4 PBS+10 mmol/L GSH.

Fig.4 Cell viability of D2A2(A) and free CBP+D2A2Pt80(B)

Fig.5 Flow cytometry histogram profile of D2A2Pt80 on cancer cellular uptake in vitro

Fig.6 Mean fluorescence intensity vs. different incubating time

Fig.7 CLSM images of OVCar-3 cells treated with FD2A2Pt80 for different incubating time

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