Regulating Twisted Skeleton to Construct Organ‐Specific Perylene for Intensive Cancer Chemotherapy

Abstract

The systemic use of pharmaceutical drugs for cancer patients is a compromise between desirable therapy and side effects because of the intrinsic shortage of organ‐specific pharmaceutical drug. Design and construction of pharmaceutical drug to achieve the organ‐specific delivery is thus desperately desirable. We herein regulate perylene skeleton to effect organ‐specificity and present an example of lung‐specific distribution on the basis of bay‐twisted PDIC‐NC. We further demonstrate that PDIC‐NC can target into mitochondria to act as cellular respiration inhibitor, inducing insufficient production of adenosine triphosphate, promoting endogenous H2O2 and .OH burst, elevating calcium overload, efficiently triggering the synergistic apoptosis, autophagy and endoplasmic reticulum stress of lung cancer cells. The antitumor performance of PDIC‐NC is verified on in vivo xenografted, metastasis and orthotopic lung cancer, presenting overwhelming evidences for potentially clinical application. This study contributes a proof‐of‐concept demonstration of twisted perylene to well attain lung‐specific distribution, and meanwhile achieves intensive lung cancer chemotherapy.

Distribution- and Metabolism-Based Drug Discovery: A Potassium-Competitive Acid Blocker as a Proof of Concept

“…Conventional pharmacochemical strategies often lead to the pursuit of drugs with a low clearance rate and high systemic exposure, and high systemic exposure to administered drugs and their metabolites often results in unrelated and undesired activity at sites beyond the target and induce toxicity. Undertaking predictable and rational drug design for targeting specific organs and constructing drugs to achieve an organ-specific distribution remain challenging, and many improvements are necessary [ 48 ]. Currently, organ-specific drug distribution can be achieved only through topical administration or indirect drug delivery strategies [ 48 ].…”

“…Undertaking predictable and rational drug design for targeting specific organs and constructing drugs to achieve an organ-specific distribution remain challenging, and many improvements are necessary [ 48 ]. Currently, organ-specific drug distribution can be achieved only through topical administration or indirect drug delivery strategies [ 48 ]. Therefore, we present a proof-of-concept example of the use of TNMDD to develop a new P-CAB.…”

“…Of course, when applied to other organs, the premise of our strategy is that an in-depth understanding of the tissue niche of the target organ is needed, and “directing and positioning group” that does not impair the activity is also essential. For example, due to the strong cation-anion interactions between the dipalmitoylphosphatidylcholine (DPPC), the chief pulmonary surfactant located in the alveolar fluid-air interface, and polyamines, polyamines can be specifically distributed in the lung, and thus, it could serve as directing and positioning groups for lung-specific drugs [ 48 , 49 ]. We believe, with the in-depth study of tissue niches in different organs, such as the eye, bone, intestines, nasal mucosa, and lung, our DMBDD strategy would promote the development of highly efficient, organ-specific drugs with low toxicity.…”

A perylene diimide-based fluorescent probe for the selective detection of hypochlorite in living cells

“…47,50–53 Recent studies have demonstrated that nonplanar PDI compounds have superior water solubility and better biological applications than planar PDI and its derivatives due to the weakening π–π interaction between adjacent molecules caused by twisted skeleton structures. 54 Besides, it has been confirmed that the functional groups at the imide-region of PDI also play a vital role in controlling the molecular packing, solubility, and optoelectronic properties of PDI derivatives. 53,55–58 Specifically, imidazole-based thiones exhibit excellent pharmacological activity and GPx-like catalytic activity, and have been proven to be an important class of compounds in today's supramolecular chemistry.…”

Comprehensive Analysis of Alteration Landscape and Its Clinical Significance of Mitochondrial Energy Metabolism Pathway‐Related Genes in Lung Cancers

“…The acid-activated mitochondria-targeting and redox-responsive nanomicelles could be a new hope for cancer treatment. Some studies found that PDIC-NC might target mitochondria as a respiratory inhibitor, induce ATP production deficiency, increase calcium overload, and effectively trigger the synergistic apoptosis of lung cancer cells [ 26 ]. Also, the use of powerful antioxidants to reduce oxidative stress has been used to prevent cancer [ 27 ].…”