Bone-targeted erythrocyte-cancer hybrid membrane-camouflaged nanoparticles for enhancing photothermal and hypoxia-activated chemotherapy of bone invasion by OSCC

Hongying Chen,Zhixiang Jian,Xintong Yao,Hongwei Dai,Yungang He,Hanyue Li,Jingqing Zhang,Jiang Deng,Yi Tang,Xiaoqing Zhang

doi:10.1186/s12951-021-01088-9

Abstract

BackgroundJaw bones are the most common organs to be invaded by oral malignancies, such as oral squamous cell carcinoma (OSCC), because of their special anatomical relationship. Various serious complications, such as pathological fractures and bone pain can significantly decrease the quality of life or even survival outcomes for a patient. Although chemotherapy is a promising strategy for bone invasion treatment, its clinical applications are limited by the lack of tumor-specific targeting and poor permeability in bone tissue. Therefore, it is necessary to develop a smart bone and cancer dual targeting drug delivery platform.ResultsWe designed a dual targeting nano-biomimetic drug delivery vehicle Asp8[H40-TPZ/IR780@(RBC-H)] that has excellent bone and cancer targeting as well as immune escape abilities to treat malignancies in jaw bones. These nanoparticles were camouflaged with a head and neck squamous cell carcinoma WSU-HN6 cell (H) and red blood cell (RBC) hybrid membrane, which were modified by an oligopeptide of eight aspartate acid (Asp8). The spherical morphology and typical core-shell structure of biomimetic nanoparticles were observed by transmission electron microscopy. These nanoparticles exhibited the same surface proteins as those of WSU-HN6 and RBC. Flow cytometry and confocal microscopy showed a greater uptake of the biomimetic nanoparticles when compared to bare H40-PEG nanoparticles. Biodistribution of the nanoparticles in vivo revealed that they were mainly localized in the area of bone invasion by WSU-HN6 cells. Moreover, the Asp8[H40-TPZ/IR780@(RBC-H)] nanoparticles exhibited effective cancer growth inhibition properties when compared to other TPZ or IR780 formulations.ConclusionsAsp8[H40-TPZ/IR780@(RBC-H)] has bone targeting, tumor-homing and immune escape abilities, therefore, it is an efficient multi-targeting drug delivery platform for achieving precise anti-cancer therapy during bone invasion.Graphical

Highlights

Jaw bones are the most common organs to be invaded by oral malignancies, such as oral squamous cell carcinoma (OSCC), because of their special anatomical relationship
These results indicate weakening of FÖrster resonance energy transfer (FRET) process in the original DiO/DiI stained WSU-HN6 membrane due to interluding of the two cell membrane segments
Immunogold labeled Transmission electron microscopy (TEM) imaging revealed analogous spherical nanoparticles, which contained two classes of colloidal golds with different sizes on the surface (Fig. 1b). These results indicated that the single Oligopeptide of eight aspartate (Asp8)[H40-PEG@ (RBC-H)] nanoparticle exhibited both red blood cell (RBC) and WSUHN6 characteristic membrane protein markers

Summary

Introduction

Jaw bones are the most common organs to be invaded by oral malignancies, such as oral squamous cell carcinoma (OSCC), because of their special anatomical relationship. Various serious complications, such as pathological fractures and bone pain can significantly decrease the quality of life or even survival outcomes for a patient. Due to the specific anatomical relationship between soft tissues and the jaw bones in the oral cavity, bone invasion has become one of the most frequent complication of oral squamous cell carcinoma (OSCC) [1,2,3]. Surgery and chemotherapy are treatment options for bone invasion by OSCC, they do not exhibit satisfactory outcomes [6]. A combined approach that can target both the damaging microenvironment of bone and the OSCC cells, will provide superior therapeutic effects than the single therapeutic options and improve the prognosis of advance OSCC [7]

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