Self‐Amplifying Nanotherapeutic Drugs Homing to Tumors in a Manner of Chain Reaction

Abstract

Active tumor‐targeting drug delivery has great potency in cancer therapy. However, the targeting efficiency of traditional active tumor‐targeting nanotherapeutic drugs is limited by the scarcity of their accessible targets/receptors in tumors. Here, a novel self‐amplifying tumor‐targeting strategy with a chain reaction mechanism is developed. A coagulation targeting peptide (GNQEQVSPLTLLKXC, termed A15)‐decorated poly(L‐glutamic acid)‐graft‐maleimide poly(ethylene glycol)/combretastatin A4 conjugate (A15‐PLG‐CA4) is prepared to obtain a self‐amplifying nanotherapeutic platform homing to tumors. After administration to tumor‐bearing mice, A15‐PLG‐CA4 starts a chain reaction cycle consisting of intratumoral hemorrhage, target FXIIIa amplification, blood clot binding, and CA4 release in tumors. In this way, A15‐PLG‐CA4 increases the level of its accessible targets (FXIIIa) in a manner of chain reaction. The FXIIIa activity at 8 h is 4.1‐fold more than the one at 0 h in the C26 tumors treated with A15‐PLG‐CA4. The total CA4 concentration at 24 h is 2.9‐fold more than the control. A15‐PLG‐CA4 shows a significantly higher antitumor effect against large C26 tumors (≈500 mm3) thanks to the remarkable tumor‐targeting ability compared with the control. Therefore, this report highlights the potential of the self‐amplifying tumor‐targeting strategy in the development of next generation active tumor‐targeting nanotherapeutic drugs for tumor therapy.

Implantable Sandwich-like Scaffold/Fiber Composite Spatiotemporally Releasing Combretastatin A4 and Doxorubicin for Efficient Inhibition of Postoperative Tumor Recurrence

“…Thereby, to further elevate the tumor recurrence inhibition, suppressing the proliferation of the peripheral tumor cells by a combined alternative drug would be promising. 25,32,33 Doxorubicin (DOX) is a classic chemotherapeutic drug that has been studied for decades, 34−36 presenting satisfactory antitumor ability via intercalating into DNA and disrupting the DNA pairs. Consequently, sequentially releasing CA4 and DOX to completely inhibit the tumor growth in the central and peripheral areas might provide great potential in elevating tumor eradiation.…”

“…Previous reports also have evidenced that a single type of chemotherapeutic drug in a safe dose normally exhibited insufficient capability to inhibit tumor recurrence, , which was frequently seen in CA4 administration for cancer therapy. , Deep into the mechanism of vascular disruption, CA4 specifically binds to tubulin and subsequently depolymerizes the microtubule of the vascular endothelial cells, which eventually cuts off the blood flow into the central area of the solid tumor, preferentially enhancing the inhibition of central tumor growth. Thereby, to further elevate the tumor recurrence inhibition, suppressing the proliferation of the peripheral tumor cells by a combined alternative drug would be promising. ,, Doxorubicin (DOX) is a classic chemotherapeutic drug that has been studied for decades, − presenting satisfactory antitumor ability via intercalating into DNA and disrupting the DNA pairs. Consequently, sequentially releasing CA4 and DOX to completely inhibit the tumor growth in the central and peripheral areas might provide great potential in elevating tumor eradiation.…”

Driving Forces Sorted In Situ Size‐Increasing Strategy for Enhanced Tumor Imaging and Therapy

“…Indeed, only a small number of NPs can effectively penetrate and retard in the tumor to promote their function after systemic administration, while most NPs accumulate in the liver and spleen through nonspecific uptake, which greatly limits their development. [34,35] Therefore, designing NPs that can achieve high accumulation, deep penetration, and long retention appear to be particularly important for improving the therapeutic efficacy. As the basic feature of NPs, particle size is essential for regulating the entire delivery process in vivo.…”

In Vivo Anchoring Bis‐Pyrene Probe for Molecular Imaging of Early Gastric Cancer by Endoscopic Techniques

“…[ 21 , 22 , 23 , 24 , 25 ] Supramolecular chemistry, a new term in recent years, involved the structural evolution of molecular self‐assemblies via noncovalent interactions supported by the exploration of functional nanomaterials in biomedicine. [ 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 ] Being dynamic in nature and presenting responsive behavior associated with supramolecular chemistry, [ 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ] “in vivo self‐assembly” could be achieved for constructing nanomaterials in situ in vivo with improved biological effects. [ 42 , 43 , 44 , 45 , 46 ] Recently, we concentrated on binding‐induced fibrillogenesis of peptide‐based nanomaterials to transform nanofibers with β ‐sheet structures in situ in vivo for targeting aggregation and efficient retention in tumors.…”