Codelivery of SH-aspirin and curcumin by mPEG-PLGA nanoparticles enhanced antitumor activity by inducing mitochondrial apoptosis

Figures & data

Figure 1 Molecular structures of curcumin and SH-aspirin.

Notes: (A) Curcumin; (B) SH-aspirin.

Table 1 Characterization of the prepared SH-ASA/Cur nanoparticles

Sample	Solvent	Drug: polymera	EEA (%)	EEC (%)	Size (nm)	PDI	DLA (%)	DLC (%)	Stability
S1	Chloroform	1:20	80±3.12	92.76±4.56	387.6±31.3	0.418±0.047	3.09±0.08	0.93±0.01	2 hours
S2	Dichloromethane	1:20	92.65±4.26	90.84±4.23	284±18.6	0.286±0.028	3.51±0.06	0.90±0.02	24 hours
S3	Ethyl acetate	1:20	83.17±3.04	87.3±3.68	122.3±6.8	0.179±0.016	3.15±0.05	0.88±0.05	72 hours
S4	Ethyl acetate	1:5	35.06±2.76	40.74±2.45	271.6±13.6	0.402±0.02	5.12±0.13	1.65±0.11	<10 minutes
S5	Ethyl acetate	1:10	70.82±4.43	79.71±5.88	172.2±8.8	0.276±0.012	5.38±0.14	1.53±0.09	4 hours
S7	Ethyl acetate	1:30	89.56±3.56	94.12±3.14	107.1±2.3	0.171±0.016	2.21±0.05	0.74±0.02	>96 hours

Notes:

a In feed; Data is presented as mean ± standard deviation.

Abbreviations: SH-ASA, SH-aspirin; Cur, curcumin; EEA, entrapment efficiency of aspirin; EEC, entrapment efficiency of curcumin; PDI, polydispersity index; DLA, drug-loading efficiency of aspirin; DLC, drug-loading efficiency of curcumin.

Figure 2 Structure of an SH-ASA/curcumin-coloaded mPEG-PLGA nanoparticle.

Abbreviations: mPEG-PLGA, methoxy poly(ethylene glycol)-poly (lactide-coglycolide); SH-ASA, SH-aspirin.

Figure 3 Characterization of SH-ASA/Cur-coloaded mPEG-PLGA nanoparticles.

Notes: (A) Size distribution; (B) zeta potential; (C) TEM image.

Abbreviations: SH-ASA, SH-aspirin; Cur, curcumin; mPEG-PLGA, methoxy poly(ethylene glycol)-poly (lactide-coglycolide); TEM, transmission electron microscope.

Figure 4 Characterization of SH-ASA/Cur-coloaded mPEG-PLGA NPs.

Notes: (A) DSC curves of blank NPs, Cur NPs, SH-ASA NPs, SH-ASA/Cur-coloaded NPs, SH-ASA NPs physically mixed with free Cur, Cur NPs mixed with free SH-ASA, and blank NPs mixed with both free drugs. (B) In vitro drug release behaviors of SH-ASA/Cur-coloaded mPEG-PLGA NPs.

Abbreviations: NP, nanoparticle; Cur, curcumin; SH-ASA, SH-aspirin; h, hours; mPEG-PLGA, methoxy poly(ethylene glycol)-poly (lactide-coglycolide); DSC, differential scanning calorimeter.

Figure 5 Uptake by SKOV3 cells.

Abbreviations: DAPI, 4′,6-diamidino-2-phenylindole; Cur, curcumin; SH-ASA, SH-aspirin.

Figure 6 Uptake by ES-2 cells.

Abbreviations: DAPI, 4′,6-diamidino-2-phenylindole; Cur, curcumin; SH-ASA, SH-aspirin.

Figure 7 Anticancer abilities of free SH-ASA and Cur on ES-2 and SKOV3 human ovarian cancer cells in vitro.

Notes: (A) ES-2 cells; (B) SKOV3 cells.

Abbreviations: SH-ASA, SH-aspirin; Cur, curcumin.

Figure 8 Anticancer effect of free SH-ASA and Cur combination.

Note: The results of the 1:4 and 1:6 combination groups demonstrated obvious synergistic effects.

Abbreviations: SH-ASA, SH-aspirin; Cur, curcumin.

Figure 9 Anticancer abilities of different formulations containing SH-ASA and/or Cur against SKOV3 and ES-2 cells after treatment for 48 hours.

Notes: (A) SKOV3 cells; (B) ES-2 cells.

Abbreviations: SH-ASA, SH-aspirin; NPs, nanoparticles; Cur, curcumin.

Figure 10 SH-ASA/Cur-coloaded mPEG-PLGA NPs induced apoptosis in human ovarian cancer cells.

Notes: (A) Control; (B) SH-ASA NPs; (C) Cur NPs; (D) SH-ASA/Cur NPs; (E) the early (Q4 region) and later (Q2 region) apoptosis rates of different formulations.

Abbreviations: FITC-A, Annexin V–fluorescein isothiocyanate; SH-ASA, SH-aspirin; NPs, nanoparticles; Cur, curcumin; mPEG-PLGA, methoxy poly(ethylene glycol)-poly (lactide-coglycolide).

Figure 11 SH-ASA/Cur-codelivery mPEG-PLGA nanoparticles demonstrated a stronger effect when activating the mitochondrial-based apoptosis signaling pathway than did the single-drug formulation, suggesting that this might be a possible explanation for the synergistic anticancer effects.

Abbreviations: Cur, curcumin; NPs, nanoparticles; SH-ASA, SH-aspirin; mPEG-PLGA, methoxy poly(ethylene glycol)-poly (lactide-coglycolide).