Opportunities and delusions regarding drug delivery targeting pancreatic cancer-associated fibroblasts

Liu, Huiqin; Shi, Yu; Qian, Feng

doi:10.1016/j.addr.2021.02.012

Cited by 44 publications

(48 citation statements)

References 119 publications

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“…PDGL-GEM@CAP/CQ also preserved paxillin levels while down-regulating MMP-2 and IL-6 as well as inhibiting activation of tumor-associated fibroblasts (Figure 8 D). These results provide further in vivo support for the idea that PDGL-GEM@CAP/CQ inhibits fibrosis in pancreatic tumors and reduces communication between tumor cells and adjacent fibroblasts, which is important for tumor growth and metastasis 32 .…”

Section: Resultssupporting

confidence: 65%

Co-delivery of autophagy inhibitor and gemcitabine using a pH-activatable core-shell nanobomb inhibits pancreatic cancer progression and metastasis

Chen

Yuan

et al. 2021

Theranostics

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Background: Metastasis is one of the main reasons for the high mortality associated with pancreatic ductal adenocarcinoma (PDAC), and autophagy regulates the metastatic migration of tumor cells, their invasion of tissues, and their formation of focal adhesions. Inhibiting autophagy may suppress tumor growth and metastasis, but the abundant extracellular matrix hinders the deep penetration of therapeutic agents. Methods: To enhance the penetration of drugs that can inhibit metastasis of pancreatic cancer, a pH-responsive drug delivery system was formulated. Gemcitabine (GEM), a first-line chemotherapeutic drug against PDAC, was loaded in 6PA-modified DGL (PDGL) nanoparticles to afford PDGL-GEM. Then PDGL-GEM was co-precipitated with the autophagy inhibitor chloroquine phosphate (CQ) and calcium phosphate to formulate PDGL-GEM@CAP/CQ. The size and morphology of the resulting “nanobomb” PDGL-GEM@CAP/CQ were characterized, and their uptake into cells, cytotoxicity and ability to inhibit autophagy were analyzed at pH 6.5 and 7.4. The anti-tumor and anti-metastasis effects of the nanobomb were explored on mice carrying Pan 02 pancreatic tumor xenografts or orthotopic tumors. Results: The pH-induced dissolution of calcium phosphate facilitated the release of CQ from the nanobomb and deep penetration of PDGL-GEM. The internalization of PDGL-GEM and subsequent intracellular release of GEM inhibited tumor growth, while CQ downregulated autophagy in tumor cells and fibroblasts. In fact, inhibition of xenograft and orthotopic tumor growth was greater with the complete PDGL-GEM@CAP/CQ than with subassemblies lacking GEM or CQ. More importantly, mechanistic studies in vitro and in vivo suggested that the nanobomb inhibits metastasis by downregulating MMP-2 and paxillin, as well as reducing fibrosis. Conclusion: The pH-sensitive PDGL-GEM@CAP/CQ shows potential for inhibiting proliferation and metastasis of pancreatic cancer through an autophagy-dependent pathway.

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Section: Resultssupporting

confidence: 65%

Co-delivery of autophagy inhibitor and gemcitabine using a pH-activatable core-shell nanobomb inhibits pancreatic cancer progression and metastasis

Chen

Yuan

et al. 2021

Theranostics

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“…Owing to its molecular variations and consequential cellular effects, it has expanded extensive courtesy in terms of public health. Cancer involves several types that cause adversative consequences, e.g., leading to the growth of a cell mass with the capability to penetrate adjacent normal tissues and move to new locations via a mechanism known as metastasis ( Figure S1 ) [ 64 , 65 ]. Figure S2 shows a detailed metastasis to new locations in (A) lungs and (B) brain shown in Figure S1 .…”

Section: Bioactivities—an Overviewmentioning

confidence: 99%

Exploring Marine as a Rich Source of Bioactive Peptides: Challenges and Opportunities from Marine Pharmacology

et al. 2022

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This review highlights the underexplored potential and promises of marine bioactive peptides (MBPs) with unique structural, physicochemical, and biological activities to fight against the current and future human pathologies. A particular focus is given to the marine environment as a significant source to obtain or extract high-value MBPs from touched/untouched sources. For instance, marine microorganisms, including microalgae, bacteria, fungi, and marine polysaccharides, are considered prolific sources of amino acids at large, and peptides/polypeptides in particular, with fundamental structural sequence and functional entities of a carboxyl group, amine, hydrogen, and a variety of R groups. Thus, MBPs with tunable features, both structural and functional entities, along with bioactive traits of clinical and therapeutic value, are of ultimate interest to reinforce biomedical settings in the 21st century. On the other front, as the largest biome globally, the marine biome is the so-called “epitome of untouched or underexploited natural resources” and a considerable source with significant potentialities. Therefore, considering their biological and biomedical importance, researchers around the globe are redirecting and/or regaining their interests in valorizing the marine biome-based MBPs. This review focuses on the widespread bioactivities of MBPs, FDA-approved MBPs in the market, sustainable development goals (SDGs), and legislation to valorize marine biome to underlying the impact role of bioactive elements with the related pathways. Finally, a detailed overview of current challenges, conclusions, and future perspectives is also given to satisfy the stimulating demands of the pharmaceutical sector of the modern world.

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“…Altogether, these features of different CAFs are essential to the pancreatic tumor growth, invasion, and resistance to chemotherapeutics. 43,47,48 Increasing studies have shown that the CAF targeting strategy may provide improved drug delivery into the tumor. There are a number of experimental studies which have shown the use of nanoparticles to either co-encapsulate an anti-stromal drug and chemotherapeutics into a nanoparticle or combine anti-stromal drug with a nanoparticle containing chemotherapeutic agent.…”

Section: Modulation Of Tumor Stroma Targeting Cafs To Improve Penetrationmentioning

confidence: 99%

Nanomedicine Strategies to Enhance Tumor Drug Penetration in Pancreatic Cancer

Lü¹,

Prakash²

2021

IJN

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Pancreatic cancer is one of the most malignant tumors with one of the worst survival rates due to its insidious onset and resistance to therapies. Most therapeutics show a desired anticancer effect in vitro; however, very poor efficacy in vivo because of the limited drug delivery and penetration into pancreatic tumors attributed to the abundance of the tumor stroma, ie, the fibrotic tumor microenvironment surrounding the cancer cells. For a better understanding of the challenges posed by the pancreatic tumor stroma, we outline the key features of the tumor microenvironment. Then we highlight major strategies used to tackle the challenges to improve drug penetration into the tumor and achieve enhanced efficacy (pre)clinically. Furthermore, we describe nanomedicine strategies to modulate the tumor stroma, degrade the extracellular matrix, and co-deliver multi-functional drugs, to improve the chemotherapeutics delivery and penetration into pancreatic tumors.

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Opportunities and delusions regarding drug delivery targeting pancreatic cancer-associated fibroblasts

Cited by 44 publications

References 119 publications

Co-delivery of autophagy inhibitor and gemcitabine using a pH-activatable core-shell nanobomb inhibits pancreatic cancer progression and metastasis

Co-delivery of autophagy inhibitor and gemcitabine using a pH-activatable core-shell nanobomb inhibits pancreatic cancer progression and metastasis

Exploring Marine as a Rich Source of Bioactive Peptides: Challenges and Opportunities from Marine Pharmacology

Nanomedicine Strategies to Enhance Tumor Drug Penetration in Pancreatic Cancer

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