Overcoming multidrug resistance through co-delivery of ROS-generating nano-machinery in cancer therapeutics

Kankala, Ranjith Kumar; Tsai, Pei-Yu; Kuthati, Yaswanth; Wei, Pei‐Ru; Liu, Chen‐Lun; Lee, Chia‐Hung

doi:10.1039/c6tb03146c

Cited by 85 publications

(68 citation statements)

References 61 publications

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“…In addition to the BLM family of therapeutics, small molecules such as hydralazine, doxorubicin, and ascorbic acid have also been shown to produce radical oxygen species (ROS) through various mechanisms upon interaction with Cu(II) (28,29). Controlled ROS generation can provide a potent means of damage in tumor cells; however, when unregulated, it can lead to significant problems in healthy cells (30).…”

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confidence: 99%

Metal-mediated diradical tuning for DNA replication arrest via template strand scission

Porter

Lindahl

Lietzke

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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) for Cu(PyED)·2Cl, indicating three nitrogens and a chloride in the psuedo-equatorial plane with the remaining pyridine nitrogen and solvent in axial positions. EPR spectra of the Cu(II) complexes exhibit an axially elongated octahedron. This spectroscopic evidence, together with density functional theory computed geometries, suggest six-coordinate structures for Cu(II) and Fe(II) complexes and a five-coordinate environment for Zn(II) analogs. Bergman cyclization via thermal activation of these constructs yields benzannulated product indicative of diradical generation in all complexes within 3 h at 37°C. A significant metal dependence on the rate of the reaction is observed [Cu(II) > Fe(II) > Zn(II)], which is mirrored in in vitro DNA-damaging outcomes. Whereas in situ chelation of PyED leads to considerable degradation in the presence of all metals within 1 h under hyperthermia conditions, Cu(II) activation produces >50% compromised DNA within 5 min. Additionally, Cu(II) chelated PyED outcompetes DNA polymerase I to successfully inhibit template strand extension. Exposure of HeLa cells to Cu(PyBD)·SO 4 (IC 50 = 10 μM) results in a G2/M arrest compared with untreated samples, indicating significant DNA damage. These results demonstrate metal-controlled radical generation for degradation of biopolymers under physiologically relevant temperatures on short timescales. metal-mediated radicals | DNA degradation | polymerase inhibition | enediyne | Bergman cyclization

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confidence: 99%

Metal-mediated diradical tuning for DNA replication arrest via template strand scission

Porter

Lindahl

Lietzke

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…The pH‐responsive complexes were encapsulated in the LDHs by using the ion‐exchange process, as presented in the previous reports . Pristine LDHs and hydrazone‐Dox complexes were added to methanol at a ratio of 5:1 and the pH of the mixture was adjusted to 9 for efficient loading of these complexes into the LDH nanocontainers.…”

Section: Methodsmentioning

confidence: 99%

“…Samples were collected, and the amount of released drug was analyzed at the respective wavelength (λ max of Dox – 480 nm). The amount of released drug was determined by periodically measuring the concentration of Dox …”

Section: Methodsmentioning

confidence: 99%

“…However, among all, precursors with NO 3 − species are most appropriate for ion‐exchange process due to their easy displacement from the interlayers . These 2D matrices possessing an overall positively charged surface not only facilitate the accommodation of negatively charged drug species in their interlayer gallery but also augment the cell internalization efficiency of such compounds through establishing the interactions with the biological membrane . More often, the LDHs facilitate the encapsulation of anionic drugs that with carboxylic functional groups, which could be difficult to encapsulate Dox in their gallery space.…”

Section: Introductionmentioning

confidence: 99%

“…) of Dox molecules facilitating their specific release of Dox in the acidic microenvironment of tumor . On the other hand, the 2D LDH matrices were prepared by the hydrothermal‐assisted co‐precipitation of Mg and Al salts in the alkaline conditions . Due to their enormous ability to exchange anions in the intergallery spaces, the pH‐responsive Hydrazone‐Dox complexes were then encapsulated within the LDH matrices via the ion‐exchange approach.…”

Section: Introductionmentioning

confidence: 99%

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Engineered pH‐responsive hydrazone‐carboxylate complexes‐encapsulated 2D matrices for cathepsin‐mediated apoptosis in cancer

Liu

Kankala

Liao

et al. 2019

J Biomedical Materials Res

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Spurred by the current advancements in engineering various intelligent nanoparticle‐based drug delivery systems, conjugation of drugs with the stimuli‐responsive molecular switches has become one of the most efficient approaches to deliver a drug cargo in spatiotemporal controlled fashions. In this study, we fabricated an innovative pH‐triggered hydrazone‐carboxylate complex of doxorubicin (Dox), which was subsequently encapsulated in the layered double hydroxide (LDH) nanoparticles for effective cancer therapeutics. These two‐dimensional (2D) biodegradable matrices efficiently delivered Dox by pH‐triggered release in the acidic lysosomal environment and their subsequent escape to cytosol. Moreover, the delivered Dox molecules and high positively‐charged surfaces of LDHs facilitated the cancer cell ablation via enhancing the cathepsins‐mediated cell apoptosis assisted by free radical species generation. The critical advancements in the nanoparticle‐based designs and substantial ablation of tumor cells through a free radical attack indicate that the designed pH‐triggered drug composites can be used for efficient cancer therapeutics. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1184–1194, 2019.

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Metal Species–Encapsulated Mesoporous Silica Nanoparticles: Current Advancements and Latest Breakthroughs

Kankala

Zhang

Liu

et al. 2019

Adv Funct Materials

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124

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Despite their advantageous morphological attributes and attractive physicochemical properties, mesoporous silica nanoparticles (MSNs) are merely supported as carriers or vectors for a reason. Incorporating various metal species in the confined nanospaces of MSNs (M-MSNs) significantly enriches their mesoporous architecture and diverse functionalities, bringing exciting potentials to this burgeoning field of research. These incorporated guest species offer enormous benefits to the MSN hosts concerning the reduction of their eventual size and the enhancement of their performance and stability, among other benefits. Substantially, the guest species act through contributing to reduced aggregation, augmented durability, ease of long-term storage, and reduced toxicity, attributes that are of particular interest in diverse fields of biomedicine. In this review, the first aim is to discuss the current advancements and latest breakthroughs in the fabrication of M-MSNs, emphasizing the pros and cons, the confinement of various metal species in the nanospaces of MSNs, and various factors influencing the encapsulation of metal species in MSNs. Further, an emphasis on potential applications of M-MSNs in various fields, including in adsorption, catalysis, photoluminescence, and biomedicine, among others, along with a set of examples is provided. Finally, the advances in M-MSNs with perspectives are summarized.(2-5 nm), tunable sizes (50-150 nm), shapes (hexagonal, wormhole-like, cubic, and lamellar) and morphologies (spheres, helical fibers, tubules, gyroids, crystals, and numerous other hierarchical complex architectures), ease of surface functionalization (both interior as well as exterior), unique topology, colloidal and thermal stabilities, and high dispersity. [4] The exceptional topology of surfactant-templated MSNs makes them unique with desirable properties that can be obtained by controlling the preparation conditions, such as the reaction temperature, pH value, stirring speed, and type of silica source, as well as surfactant, among others. [4j,m,n,5] These advantages make the MSNs as versatile materials and ideal choice for catalysis, [6] adsorption, [7] optical devices, [4j] polymeric fillers, [8] and diverse biomedical applications including bio-imaging, [4r,t,u,9] biocatalysts, [10] biosensing, [11] tissue engineering, [4f ] and drug/ gene delivery accounting for targeted and controlled release systems. [3d,4i,o-t,v,12] With these significant advantages and attractive physicochemical properties, it is highly anticipated to harness the desirable and beneficial properties of MSNs through the incorporation of various metals and their respective conjugates for exploration in innovative applications with exceptional performance. [13] The encapsulated metal species in the confined nanospaces of MSNs (M-MSNs) not only significantly enrich the mesoporous architecture and functionalities of MSN, but also tend to overcome their intrinsic limitations, such as their poor suspension ability and stability, lack of intrig...

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Overcoming multidrug resistance through co-delivery of ROS-generating nano-machinery in cancer therapeutics

Abstract: The use of nanotechnology to overcome multidrug resistance (MDR) in cancer cells has been predominant.

Cited by 85 publications

References 61 publications

Metal-mediated diradical tuning for DNA replication arrest via template strand scission

Metal-mediated diradical tuning for DNA replication arrest via template strand scission

Engineered pH‐responsive hydrazone‐carboxylate complexes‐encapsulated 2D matrices for cathepsin‐mediated apoptosis in cancer

Metal Species–Encapsulated Mesoporous Silica Nanoparticles: Current Advancements and Latest Breakthroughs

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