Ultrasonic Cavitation‐Assisted and Acid‐Activated Transcytosis of Liposomes for Universal Active Tumor Penetration

Abstract

Active tumor penetration has been recently recognized as a promising strategy to resolve the limitation of nanomedicine in terms of tumor penetration, but it is challenging to develop active transporting nanocarriers. Here, an ultrasonic cavitation‐assisted and acid‐activatable active transporting liposome for a broad range of tumors is reported. The active transporting liposome (size and charge dual‐conversional gemcitabine prodrug‐integrated liposomal nanodroplet (SCGLN)) overcomes the tight blood vessel walls with the aid of ultrasonic cavitation. The SCGLN subsequently transforms from micro‐size to nano‐size under prolonged ultrasound radiation. Once in the acidic tumor microenvironment, the nanosized SCGLN undergoes negative‐to‐positive charge‐reversal and triggers the cationization‐initiated transcytosis to penetrate deep into tumor parenchyma. The gemcitabine‐loaded SCGLN exhibits potent antitumor activity in multiple poorly permeable tumor models, which completely erases subcutaneous U251 glioma and stops the progression of orthotopic BxPC3 pancreatic ductal adenocarcinoma. This study presents a promising and universal strategy to develop active penetrating nanomedicines for efficient drug delivery in the low permeable tumor.

ZIF-based carbon dots with lysosome-Golgi transport property as visualization platform for deep tumour therapy via hierarchical size/charge dual-transform and transcytosis

“…Firstly, we measured the zeta potential of ZCD under different pH values, given that cationization could promote the transport of nanoparticles to the Golgi apparatus and transcytosis. 39,40 As shown in Fig. S11,† the zeta potential of ZCD was −38 ± 3.9 mV at pH 7.4, which changed to 1.0 ± 0.6 mV at pH 6.5 and 8.9 ± 1.2 mV at pH 5.0.…”

“…33,34 Recently, many studies have shown that positively charged macromolecules and nanoparticles can target the Golgi apparatus and be transported out of cells. [35][36][37][38][39][40] With the assistance of the Golgi apparatus, macromolecules and nanoparticles with a positive charge can reach distal tumour cells and release the loaded drugs via continuous cycles of endocytosis-transcytosis-exocytosis. 41 Therefore, targeting the Golgi apparatus provides another way to effectively improve the penetration of nanoparticles into deep tumours.…”

An excipient-free “sugar-coated bullet” for the targeted treatment of orthotopic hepatocellular carcinoma

“…Nanomedicine provides a promising opportunity to improve the clinical outcomes of traditional chemotherapeutics that often suffer from the drawbacks of poor water solubility, low tumortargeting ability, and rapid blood/renal clearance. [1][2][3] Some nanoformulations, including liposomes, [4][5][6][7] polymers. [8][9][10][11] and inorganic materials [12][13][14] that possess enhanced permeability and retention (EPR) effect show greater efficacy than free molecular drugs in the laboratory.…”

Enhanced Intracellular Transcytosis of Nanoparticles by Degrading Extracellular Matrix for Deep Tissue Radiotherapy of Pancreatic Adenocarcinoma

“…Transcytosis is an important active transport process by which biomacromolecules can be transferred through densely packed epithelial and endothelial cells, such as insulin transport across blood-brain barrier and micronutrient absorption by intestine. − Transcytosis can be initiated by specific receptors or membrane electrostatic absorption and mediated by recycling endosomes. , During transcytosis, biomacromolecules are internalized, transported across cytoplasm, and ejected out. , Recently, transcytosis has been proven as an efficient approach in elevating tumor penetration of nanoparticles for cancer therapy. , Shen et al reported that cationized polymer–drug nanoparticles exhibited a high active transcytosis capability and exerted potent inhibition against established tumors with a volume of ∼500 mm 3 . , Tao et al reported that poly- l -lysine-modified upconversion NPs with a positive surface charge can be transported into deep tissues by transcytosis . More recently, our group reported the use of a transcytosis nanopomegranate for efficient sensitization of deep tumor tissues to RT .…”

“…39,40 Shen et al reported that cationized polymer−drug nanoparticles exhibited a high active transcytosis capability and exerted potent inhibition against established tumors with a volume of ∼500 mm 3 . 41,42 Tao et al reported that poly-L-lysine-modified upconversion NPs with a positive surface charge can be transported into deep tissues by transcytosis. 43 More recently, our group reported the use of a transcytosis nanopomegranate for efficient sensitization of deep tumor tissues to RT.…”