Ultrasound-targeted microbubble destruction improves the suppression and magnetic resonance imaging of pancreatic cancer with polyethyleneimine nanogels

The chemoresistance of pancreatic cancer tumors urgently needs to be addressed. Pancreatic cancer is characterized by an abundant stroma, with significant fibrous connective tissue formation that encapsulates the tumor parenchyma and forms an interstitial microenvironment. Pancreatic stellate cells (PSCs) play a crucial role in this microenvironment and specially secrete periosteal protein (periostin), which can promote tumor growth, metastasis, and chemoresistance. Therefore, periostin has become a specific target of chemotherapy resistance intervention methods. The proposed polyethyleneimine (PEI) nanogels have multiple modification and efficient drug-loading properties. Additionally, ultrasound-targeted microbubble destruction (UTMD) supports the breakdown of the tough interstitial barrier of pancreatic cancer. A small interfering RNA (siRNA) can be used to downregulated the periostin gene, while sustained release of gemcitabine can promote killing of tumor cells. This method achieves a combination of gene silencing and chemotherapy. The imaging effect can be evaluated using magnetic resonance imaging (MRI). The ultimate goal of this work is to support individualized and effective therapeutic methods and help develop new strategies for pancreatic cancer treatment.