Pulmonary Codelivery of Doxorubicin and siRNA by pH‐Sensitive Nanoparticles for Therapy of Metastatic Lung Cancer

Abstract

A pulmonary codelivery system that can simultaneously deliver doxorubicin (DOX) and Bcl2 siRNA to the lungs provides a promising local treatment strategy for lung cancers. In this study, DOX is conjugated onto polyethylenimine (PEI) by using cis-aconitic anhydride (CA, a pH-sensitive linker) to obtain PEI-CA-DOX conjugates. The PEI-CA-DOX/siRNA complex nanoparticles are formed spontaneously via electrostatic interaction between cationic PEI-CA-DOX and anionic siRNA. The drug release experiment shows that DOX releases faster at acidic pH than at pH 7.4. Moreover, PEI-CA-DOX/Bcl2 siRNA complex nanoparticles show higher cytotoxicity and apoptosis induction in B16F10 cells than those treated with either DOX or Bcl2 siRNA alone. When the codelivery systems are directly sprayed into the lungs of B16F10 melanoma-bearing mice, the PEI-CA-DOX/Bcl2 siRNA complex nanoparticles exhibit enhanced antitumor efficacy compared with the single delivery of DOX or Bcl2 siRNA. Compared with systemic delivery, most drug and siRNA show a long-term retention in the lungs via pulmonary delivery, and a considerable number of the drug and siRNA accumulate in tumor tissues of lungs, but rarely in normal lung tissues. The PEI-CA-DOX/Bcl2 siRNA complex nanoparticles are promising for the treatment of metastatic lung cancer by pulmonary delivery with low side effects on the normal tissues.

A Smart Nano‐Prodrug Platform with Reactive Drug Loading, Superb Stability, and Fast Responsive Drug Release for Targeted Cancer Therapy

“…Hematoxylin and eosin (H&E) staining analyses showed that cRGD‐PS‐DM1 nano‐prodrug did not induce obvious damage to the major organs of treated mice (Figure S4, Supporting Information), corroborating that this nano‐prodrug formulation has a low systemic toxicity. B16F10 melanoma is known as a highly aggressive malignancy . The high treatment efficacy and low side effects of cRGD‐PS‐DM1 nano‐prodrug in B16F10 tumor‐bearing mice suggests that this nanodrug platform has a great potential for cancer chemotherapy.…”

Molybdenum disulfide/graphene oxide nanocomposites show favorable lung targeting and enhanced drug loading/tumor-killing efficacy with improved biocompatibility

“…Given that B16 murine melanoma cancer cells harbor favorable and selective propensity to metastasize to the lung, 62,63 we used this model to determine the anti-tumor effect of MoS 2 /GO by making best use of its preferential lung targeting capability. As shown in Supplementary Figure S9A, there was no significant difference in body weight among all groups, and no abnormal activities (for example, diet and moving) were observed for all mice, ruling out the occurrence of gross toxicity to mice treated with these materials.…”

Antiviral Activity of Specific siRNA against Hemagglutinin and Neuraminidase of Influenza Virus H1N1 in MDCK Cell Culture

“…siRNA expression plasmid pBabe-Super was chosen in this study, which directed the synthesis of small interfering RNAs in cells. The findings reveal that newly synthesized nucleocapsid, polymerase A (PA) and polymerase B1 (PB1) proteins are required for avian influenza virus transcription and replication and provide a basis for the development of small interfering RNAs as prophylaxis and therapy for avian influenza infection in birds and humans [24].…”