In 2022, the team of Zhang Qiang/He Bing/Dai Wenbing/Wang Xueqing made a series of progress in the field of nano-delivery

In 2022, the team of Zhang Qiang/He Bing/Dai Wenbing/Wang Xueqing of the State Key Laboratory of Natural Medicine and Biomimetic Drugs of our hospital has continuously achieved important results in the field of nanodelivery research, and has been published in Advanced Materials（IF = 32.
086）、Bioactive Materials（IF = 16.
874）、Nanoscale A series of research articles have been published in international authoritative academic journals such as Horizons (IF = 11.
684), which are briefly reviewed below
.

First, based on photocatalytic proximity labeling technology, the rapid dynamic interaction map of nanoparticles and plasma proteins was constructed

After entering the bloodstream, nanodrugs quickly interact with plasma proteins and form protein crowns on the surface of nanoparticles, which can have a wide impact
on the fate of nanodrugs in vivo.
Although a large number of studies have been conducted on protein crowns through various strategies such as centrifugation, there are still great challenges
in resolving the mechanism and dynamic structure of protein crowns at second-level time resolution.

In this study, a nanoparticle photocatalytic proximity labeling technology platform (nano-PPL) was established to analyze the mechanism and dynamic structure of in situ protein crown formation at all times
.
The nano-PPL technique is performed by constructing a co-encapsulation of the photosensitizer dihydroporphyrine e6 (Ce6) and the protein-labeled substrate biotin-phenol (BP).
The core-shell nanoparticles (NPs@CeBP) are achieved
.
The principle is: when the NPs@CeBP is irradiated by a laser, Ce6 located in the core receives energy and activates BP in the outer layer, the activated BP Free radicals can be quickly covalently coupled to proteins adsorbed on the surface of nanoparticles, and BP-tagged proteins can be identified by proteomics and other means after magnetic bead sorting
.

Nano-PPL technology increases the 30 sec time resolution of classical centrifugation strategies to 5 sec and satisfies simultaneous in situ analysis
.
In this study, ultra-high-resolution fluorescence microscopy was used to optimize and determine the labeling range of nano-PPL, and the labeled proteins were screened by bioinformatics analysis to ensure the accurate and comprehensive analysis
of protein coronavirus.
In this study, nano-PPL technology was used to construct a rapid dynamic map of protein crowns of nanoparticles with different potentials, and verified the effect of rapidly formed protein crowns on early nanoparticle-cell interactions.

In short, nano-PPL technology can be widely used in vitro detection of various nanoparticle-protein interactions, and can be extended to the study of nanoparticle-protein rapid interaction in the whole process of in the internal delivery of nanodrugs.

The paper was published in Advanced Materials, with Zhang Zibin, a 2018 direct doctoral student in the School of Pharmacy, as the first author of the paper, and Professor Zhang Qiang and Professor He Bing as co-corresponding authors
.

Second, enzyme-responsive deformable peptide-photosensitizer conjugates for photoimmunotherapy of breast cancer

Breast cancer remains a disease
with high morbidity and mortality due to its complexity and high metastasis.
Due to the good therapeutic efficacy of mild photothermal therapy combined with immune checkpoint inhibitors in the treatment of advanced or metastatic cancer, it has attracted more and more attention
from researchers.
However, integrating the two therapies and giving them clinical translational potential remains a challenge
.

In this study, a peptide-photosensitizer conjugate consisting of a PD-L1 antagonist peptide, an MMP-2-specific enzymatic hydrolysis sequence, a self-assembled polypeptide motif and the photosensitizer Purpurin 18 was designed ( PPC）
。 One-component PPCs can self-assemble to form nanoparticles and are suitable for intravenous injection
.
When this nanoparticle aggregates at the tumor site, the PPC nanoparticle is degraded by the highly expressed MMP-2 enzyme at the tumor site, thereby initiating the release of tumor-specific PD-L1 antagonist peptide
.
At the same time, the nanoparticles are gradually transformed into co-assembled nanofibers, thereby promoting the retention
of undegraded PPCs within the tumor.
In vivo studies have shown that PPC nanocarriers promote cytotoxic T lymphocyte infiltration and DC maturation under laser irradiation, thereby enabling 4T1 Tumor cells are sensitive
to immune checkpoint blocking therapy.
Therefore, PPC nanoparticles can effectively inhibit tumor growth and prevent the formation
of lung metastasis both in situ and distal.
Based on peptide self-assembly tools, this study provides a simple and effective combination strategy
for photoimmunotherapy for breast cancer.

The paper was published in Bioactive Materials, with Yanan Sun, a postdoctoral fellow in the School of Pharmacy, and Bochen Lü, a 2016 long-term student, as co-first authors of the paper, and Associate Professor Dai Wenbing, Professor Zhang Qiang and Professor Wang Xueqing as co-corresponding authors
.

Third, the binding of nanoparticles to extracellular lipid structure regulates tumor cell migration

The extracellular matrix (ECM) is one of the important components of
the tumor microenvironment.
Recent studies have found that, in addition to proteins and polysaccharides, tumor cells secrete lipid components, such as extracellular vesicles, into the tumor microenvironment
.
By synergizing with matrix proteins, these lipid structures induce recognition and uptake by peripheral cells, regulating the migration
of tumor cells.
Broadly speaking, these lipid structures can also be considered as a special extracellular matrix component
.
The incomplete and thorough understanding of the nano-ECM interaction mechanism in the current study greatly limits the effective delivery
of nanodrugs to tumor cells.

Based on the above scientific questions, the study explores the interaction characteristics
between nanomedicines and the extracellular matrix.
Through classical cell migration experiments and analysis of cell morphology and motility based on high-content imaging techniques, it was found for the first time that nanoparticles tightly bind to specific types of lipid components in the extracellular matrix, namely retraction fibers (RFs) and migrasomes
.
Migrators are organelles of a novel vesicle structure discovered in recent years that can mediate cellular function
by regulating the release of cytosolic contents.
The study found that this interaction of nanoparticles with contractile fibers and migrators changes cell morphology, limits cell range of motion and affects cell adhesion
to the substrate.
Based on these effects, nanoparticles have been shown in in vitro experiments to inhibit the migration of tumor cells, and their potential against tumor metastasis in mice has also been preliminarily confirmed
.
The findings in this study may represent a universal mechanism
for nanoparticle interactions with the extracellular matrix.
In addition, the inhibition of cell migration by the interaction of nanoparticles with contractile fibers and migrators also suggests potential targets and strategies
for anti-metastatic nanotherapy targeting these lipid structures.

The paper was published in Nanoscale Horizons, with Yuxi Cheng, a 2015 long-term student of the School of Pharmacy, as the first author of the paper, and Professor Zhang Qiang and Professor He Bing as co-corresponding authors
.

[Communication / Communication / Author / Brief / Introduction].

Professor Zhang Qiang

Distinguished Professor of Peking University, Director of Beijing Key Laboratory of Molecular Pharmacy and Drug Delivery System, Head of Innovation Team of Ministry of Education, Standing Director of Chinese Pharmaceutical Association, Vice Chairman of Nanomedicine Professional Committee of Chinese Pharmaceutical Association, Deputy Director of Pharmaceutical Professional Committee of National Pharmacopoeia Commission, Deputy Editor of Journal of Pharmacy B, Journal of Controlled Release Editorial Board Member, etc
.
As the first chairman of CRS China Chapter, he has been engaged in nanomedicine research for a long time, in Nature Nanotechnology, Advanced Materials, and Nature Communications 、Advanced Functional Materials、Nano Today、ACS Nano、Advanced Drug More than 300 articles have been published in Delivery Review, Biomaterials, Journal of Controlled Release, etc SCI papers
.
Responsible for completing more than 30 innovative preparation researches, applying for more than 50 domestic and foreign invention patents, and developing and listing a number of new drug delivery systems, generating major economic and social benefits
.
He has won many
national, provincial and ministerial scientific and technological achievement awards.

Research interests: Molecular pharmacy and clinical transformation of innovative preparations, including basic research and clinical transformation of novel delivery systems for poorly soluble drugs, anticancer drugs, and macromolecule drugs
.

Researcher He Bing

He has been engaged in nanodrug delivery research for a long time, and has been the first author or corresponding author in Advanced Materials, Advanced Drug Delivery Review, Nature Communications, He has published many research papers in authoritative journals such as Nano Today, ACS Nano, Biomaterials, and Nanoscale Horizons
。 At present, he has undertaken one project of the National Natural Science Foundation of China and participated in many research projects
such as the National 973 Program.
At home and abroad, the research on the cross-cell transport mechanism of nanodrug carriers was carried out from the perspective of nanobiology, and a series of unique transport pathways and regulatory laws of nanodrugs were elucidated, and related research was evaluated by foreign experts as "landmark research"
in the field.
In recent years, it has taken the lead in applying multi-omics technology to this field, proposed the concept and strategy of nanosystem biology at home and abroad, made many new discoveries in nano-organism interaction based on molecular level, and gradually established a nanomedicine evaluation system
with its own characteristics.

Research interests: nanobiology and molecular pharmacy, including molecular regulatory mechanisms of interaction between nanomaterials and organisms (cells), signal regulatory networks for cell transport in nanocarriers, etc
.

Associate Professor Dai Wenbing

He is currently the deputy head of the Department of Pharmacy and has long been engaged in basic and translational research
on drug delivery.
Undertake national scientific research projects such as the National Key R&D Program, the National Natural Science Foundation of China and the National New Drug Major Project; As the first or corresponding author in Advanced Functional Materials, Bioactive Materials, Journal of Extracellular Vesicles Published a number of papers in Biomaterials, Journal of Controlled Release, Advanced Drug Delivery Review and other journals; Served as the youth editorial board member of the Asian Journal of Pharmaceutical Sciences, Pharmaceutics editorial board; As the main completer, he won one second prize of National Science and Technology Progress Award and one first prize of Natural Science of the Ministry of Education; Obtained 13 domestic and foreign patent authorizations, many of which have been transferred, and obtained clinical approval for 2 improved new drugs; He has participated in the CDE new drug review meeting (chemical and biological drugs) for many times, and drafted or participated in the drafting of a number of technical guidelines
including the "Technical Guidelines for Quality Control Research of Nanomedicines".

Research Interests: Drug delivery research based on peptide self-assembly; Monoclonal antibody drug delivery; New strategies and translational research on nanotechnology of poorly soluble drugs, etc
.

Researcher Wang Xueqing

He has presided over 5 projects of the National Natural Science Foundation of China, 2 projects of the Beijing Municipal Natural Science Foundation, and participated in 973, 863, and national major new drug creation projects
for many times.
As the first author or corresponding author, he has published papers in journals such as Advanced Drug Delivery Review, Biomaterials, Journal of Controlled Release, etc More than 60 articles, authorized 7 national invention patents
.
He has won 6 provincial and ministerial awards such as the second prize of the National Science and Technology Progress Award, the first and second prizes of the Natural Science Award of the Ministry of Education, and the second prize of the Beijing Science and Technology Award
.

Research Interests: Nanomedicine transport mechanism and biological effects
across biological barriers.

【Related Literature】

1.
Zhang, Zibin, Junji Ren, Wenbing Dai, Hua Zhang, Xueqing Wang, Bing He, and Qiang Zhang.
2022.
"Fast and Dynamic Mapping of the Protein Corona on Nanoparticle Surfaces by Photocatalytic Proximity Labeling.
"  Advanced Materials n/a (n/a):2206636.
doi: https://doi.
org/10.
1002/adma.
202206636.

2.
Sun, Yanan, Bochen Lyu, Chang Yang, Bing He, Hua Zhang, Xueqing Wang, Qiang Zhang, and Wenbing Dai.
2023.
"An enzyme-responsive and transformable PD-L1 blocking peptide-photosensitizer conjugate enables efficient photothermal immunotherapy for breast cancer.
"  Bioactive Materials 22:47-59.
doi: https://doi.
org/10.
1016/j.
bioactmat.
2022.
08.
020.

3.
Cheng, Yuxi, Junji Ren, Shumin Fan, Peiyao Wu, Wenshu Cong, Yuxing Lin, Shaojie Lan, Siyang Song, Bin Shao, Wenbing Dai, Xueqing Wang, Hua Zhang, Bo Xu, Wenzhe Li, Xia Yuan, Bing He, and Qiang Zhang .
2022.
"Nanoparticulates reduce tumor cell migration through affinity interactions with extracellular migrasomes and retraction fibers.
" Nanoscale Horizons 7 (7):779-789.
doi: https://doi.
org/10.
1039/d2nh00067a.

State Key Laboratory of Natural Medicines and Biomimetic Medicines