52P - Antitumor efficacy of polypyrrole-polyethyleneimine nanocomplex to target B-cell lymphoma

Background

Traditional administration of standard lymphoma treatment can lead to poor pharmacokinetics and poor biological distribution. Recently, the nanomaterial system shows tremendous potential for therapy with a high drug-loading efficiency, good biosafety, improved bioavailability, and active targeting. This study aimed to report novel and intelligent therapeutics with particular and targeted B-cell killing in aggressive B-cell lymphoma based on nanotechnology.

Methods

A synthetic polypyrrole-polyethyleneimine nanocomplex (PPY-PEI NC) was constructed and characterized to provide its interaction with specific target B-cell lymphoma. We further investigated cell apoptosis of PPY-PEI NC in Raji cells in vitro and Raji xenograft mice models and the loss of mitochondrial transmembrane potential by Propidium iodide, Annexin V, and Rhodamine 123 staining, respectively. In addition, protein analysis identified activation of the apoptotic signaling pathway (GSK-3β, Bax, Bcl-2, Mcl-1, PARP, caspase 3) and were examined to clarify their roles.

Results

An earlier engulfment of PPY-PEI NC rapidly targeted B-cell lymphoma in clathrin-dependent endocytosis. PPY-PEI NC effectively caused B-cell lymphoma inhibition in an intrinsic pathway of apoptosis in vitro. PPY-PEI NC decreased anti-apoptotic Bcl-2 family proteins and caused classical caspase substrate activation. PPY-PEI NC induced loss of MTP while stabilizing MTP and inhibiting caspase protected B-cells from mitochondrial apoptosis. In addition, PPY-PEI NC-activated GSK-3β and inhibiting GSK-3β prevented MTP loss and mitochondrial apoptosis. In Raji subcutaneous xenograft mice model, PPY-PEI NC not only significantly inhibited the effect on tumor growth but also demonstrated no noticeable adverse effects on the treated nude mice.

Conclusions

The PPY-PEI nanocomplex strongly showed in vitro and in vivo antitumor activities. These results suggest that PPY-PEI NC has a promising application prospect as an innovative, safe and effective anti-lymphoma agent.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

The Ministry of Science and Technology, Taiwan.

Disclosure

All authors have declared no conflicts of interest.