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Original Research

Lung Cancer Combination Treatment: Evaluation of the Synergistic Effect of Cisplatin Prodrug, Vinorelbine and Retinoic Acid When Co-Encapsulated in a Multi-Layered Nano-Platform

, &
Pages 4519-4531 | Published online: 27 Oct 2020

Figures & data

Figure 1 Synthesis of cisplatin prodrug. Cisplatin prodrug (CISP) was synthesized by conjugating the amino group of tryptophan (TRP) with the carboxylated CIS.

Figure 1 Synthesis of cisplatin prodrug. Cisplatin prodrug (CISP) was synthesized by conjugating the amino group of tryptophan (TRP) with the carboxylated CIS.

Figure 2 A multi-layered nano-platform contained CISP, VNR and ATRA were prepared and named CISP/VNR/ATRA MLNP. The TEM image showed that the CISP/VNR/ATRA MLNP was spherical particles with inner cores and coats on the outer surface.

Figure 2 A multi-layered nano-platform contained CISP, VNR and ATRA were prepared and named CISP/VNR/ATRA MLNP. The TEM image showed that the CISP/VNR/ATRA MLNP was spherical particles with inner cores and coats on the outer surface.

Figure 3 Particle sizes (A), PDIs (B), and zeta potentials (C) of the particles.

Figure 3 Particle sizes (A), PDIs (B), and zeta potentials (C) of the particles.

Figure 4 The EE (A) and LE (B) of drugs loaded particles.

Figure 4 The EE (A) and LE (B) of drugs loaded particles.

Figure 5 In vitro drug release profiles of CISP (A), VNR (B) and ATRA (C). All the three drugs showed sustained release from MLNPs. CISP and VNR exhibited similar release profiles, but ATRA were released from MLNPs in different manners compared with CISP and VNR.

Figure 5 In vitro drug release profiles of CISP (A), VNR (B) and ATRA (C). All the three drugs showed sustained release from MLNPs. CISP and VNR exhibited similar release profiles, but ATRA were released from MLNPs in different manners compared with CISP and VNR.

Figure 6 The cellular uptake efficiency of CISP/VNR/ATRA MLNP and non HA coating CISP/VNR/ATRA NP were compared by the images and quantitative results.

Figure 6 The cellular uptake efficiency of CISP/VNR/ATRA MLNP and non HA coating CISP/VNR/ATRA NP were compared by the images and quantitative results.

Figure 7 In vitro cytotoxicity. Concentration deepened manners were found in all drugs contained formulations on both A549/CIS (A) and BEAS-2B cells (B). *P < 0.05.

Figure 7 In vitro cytotoxicity. Concentration deepened manners were found in all drugs contained formulations on both A549/CIS (A) and BEAS-2B cells (B). *P < 0.05.

Figure 8 The synergistic cytotoxicity was evaluated by CI values on the bases of IC50 values of different formulations. The effect of three-drug combination treatment was compared with the effect of treatment with each drug alone.

Figure 8 The synergistic cytotoxicity was evaluated by CI values on the bases of IC50 values of different formulations. The effect of three-drug combination treatment was compared with the effect of treatment with each drug alone.

Figure 9 In vivo tumor inhibition ability of CISP/VNR/ATRA MLNP, CISP/VNR/ATRA NP and Free CISP/VNR/ATRA. *P < 0.05.

Figure 9 In vivo tumor inhibition ability of CISP/VNR/ATRA MLNP, CISP/VNR/ATRA NP and Free CISP/VNR/ATRA. *P < 0.05.

Figure 10 In vivo tissue distribution of CISP/VNR/ATRA MLNP, CISP/VNR/ATRA NP and Free CISP/VNR/ATRA. *P < 0.05.

Figure 10 In vivo tissue distribution of CISP/VNR/ATRA MLNP, CISP/VNR/ATRA NP and Free CISP/VNR/ATRA. *P < 0.05.

Figure 11 Drugs loaded nanoparticles groups presented no significant change of body weight (A). ALT (B), LDH (C), and BUN (D) levels illustrated that drugs loaded nanoparticles groups did not change the parameters compared with control groups, while free drugs caused significant increase of these data. *P < 0.05.

Figure 11 Drugs loaded nanoparticles groups presented no significant change of body weight (A). ALT (B), LDH (C), and BUN (D) levels illustrated that drugs loaded nanoparticles groups did not change the parameters compared with control groups, while free drugs caused significant increase of these data. *P < 0.05.