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. 2020 Feb 27;7(9):1485-1512.
doi: 10.1093/nsr/nwaa034. eCollection 2020 Sep.

Strategies for engineering advanced nanomedicines for gas therapy of cancer

Yingshuai Wang  1 , Tian Yang  1 , Qianjun He  1
Affiliations

Strategies for engineering advanced nanomedicines for gas therapy of cancer

Yingshuai Wang et al. Natl Sci Rev. .

Abstract

As an emerging and promising treatment method, gas therapy has attracted more and more attention for treatment of inflammation-related diseases, especially cancer. However, therapeutic/therapy-assisted gases (NO, CO, H2S, H2, O2, SO2 and CO2) and most of their prodrugs lack the abilities of active intratumoral accumulation and controlled gas release, resulting in limited cancer therapy efficacy and potential side effects. Therefore, development of nanomedicines to realize tumor-targeted and controlled release of therapeutic/therapy-assisted gases is greatly desired, and also the combination of other therapeutic modes with gas therapy by multifunctional nanocarrier platforms can augment cancer therapy efficacy and also reduce their side effects. The design of nanomedicines with these functions is vitally important, but challenging. In this review, we summarize a series of engineering strategies for construction of advanced gas-releasing nanomedicines from four aspects: (1) stimuli-responsive strategies for controlled gas release; (2) catalytic strategies for controlled gas release; (3) tumor-targeted gas delivery strategies; (4) multi-model combination strategies based on gas therapy. Moreover, we highlight current issues and gaps in knowledge, and envisage current trends and future prospects of advanced nanomedicines for gas therapy of cancer. This review aims to inspire and guide the engineering of advanced gas-releasing nanomedicines.

Keywords: cancer treatment; controlled release; drug delivery; gas therapy; nanomedicine.

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Figures

Figure 1.
Figure 1.
Strategies for engineering advanced nanomedicines for augmented gas therapy of cancer.
Figure 2.
Figure 2.
Typical gas-releasing nanomedicines constructed with exogenous stimuli-responsive GRMs. (A) Visible light-responsive Fr-MnCO nanomedicine for controlled CO release. Adapted with permission from [5]. (B) NIR light-responsive MnCO-GO nanomedicine for controlled CO release. Reprinted with permission from [7]. (C) US-responsive BNN6‐SPION@hMSN (left) and hMSN-LA-CO2 (right) nanomedicines for controlled NO and CO2 release, respectively. Reproduced with permission from [8] and [9]. (D) X-ray-responsive PEG-USMSs-SNO nanomedicine for controlled NO release. Reproduced with permission from [10]. (E) NIR photothermal-responsive SPION@PDA@MSN-SNO and FeCO@MCN-PEG nanomedicines for controlled NO/CO release, respectively. Reproduced with permission from [11] and [12]. (F) Magnetothermal-responsive IONP-MCO nanomedicine for controlled CO release. Reprinted with permission from [13].
Figure 3.
Figure 3.
Representative gas-releasing nanomedicines constructed by endogenous stimuli-responsive GRMs. (A) The H2O2-responsive Arg@MSN and MnCO@MSN nanomedicines for controlled NO and CO release, respectively. Reproduced with permission from [15] and [16]. (B) The acid-responsive AB@MSN and MBN nanomedicines for controlled H2 release. Reproduced with permission from [18] and [19]. (C) The glucose-responsive Arg@hMON-GOx nanomedicine for controlled NO release. Reproduced with permission from [20]. (D) The GSH-responsive p(GD-Az-JSK)/DOX nanomedicine for controlled NO release. Reproduced with permission from [21]. (E) The enzyme-responsive CO and NO delivery systems. Reproduced with permission from [22] and [23].
Figure 4.
Figure 4.
Representative gas-releasing nanomedicines constructed by exogenous stimuli-responsive breakable/convertible carriers. (A) NIR-responsive PdH, BNN6@GON, SP@UCNP-PEG and UCNP@hMSN-DM nanomedicines for controlled release of H2, NO, H2S and SO2, respectively. Reproduced with permission from [,–28]. (B) NIR-/UV-responsive breakable nanomedicines for controlled release of 1O2 and NO. Reproduced with permission from [29] and [30]. (C) UV-responsive decomposable DEACM-PEG nanomedicine for controlled release of CO2. Reproduced with permission from [31]. (D) Photothermal-responsive breakable GSNO/Cu1.6S-PLGA nanomedicine for controlled release of NO. Reproduced with permission from [32]. (E) Magnetic-thermal breakable nanomedicine for controlled release of NO. Reproduced with permission from [33].
Figure 5.
Figure 5.
Representative gas-releasing nanomedicines constructed by endogenous stimuli-responsive decomposable/breakable carriers. (A) GSH-responsive decomposable QM-NPQ@PDHN nanomedicine for controlled NO release. Reproduced with permission from [34]. (B) Cystine-responsive decomposable H2S-releasing nanomedicine. Reproduced with permission from [37]. (C) Acid-responsive decomposable DETANONOate@PLGA, GSNO@PEG-PAsp-CaCO3 and Ce6&DOX@HMnO-PEG nanomedicines for controlled NO and O2 release. Reproduced with permission from [38–40]. (D) Enzyme-responsive decomposable KHA-NG nanomedicine for controlled NO release. Reproduced with permission from [41].
Figure 6.
Figure 6.
Three catalysis strategies for construction of representative catalytic gas-releasing nanomedicines. (A) Photocatalytic H2-releasing HisAgCCN (above) and Chlα-AA-AuNPs@liposome (below) nanomedicines. Reprinted with permission from [44] and [45]. (B) Chemically catalytic ROS-releasing Fe nanomedicine (above), CO-releasing MnCO@Ti-MOF nanomedicine (centre) and AuNP nanomedicine (below). Reproduced with permission from [46–48]. (C) Enzymocatalytic catalase@MON (above) and β-gal-NONOate@ liposome nanomedicines (below). Reprinted with permission from [49] and [50].
Figure 7.
Figure 7.
Schematic illustration of the tissue-targeted (A) and organelle-targeted (B) delivery strategies with gas-releasing nanomedicines.
Figure 8.
Figure 8.
Representative gas-releasing nanomedicines with various targeted functions. (A) Tumor tissue-targeted Arg@hMSN-CLT1-G nanomedicine. Reproduced with permission from [15]. (B) Tumor cellular membrane-targeted DOX@KHA-NGs (left), N-GQDs/CDs/TiO2@Gal/FA-RuNO (centre) and O2@liposome-RGD (right) nanomedicines. Reproduced with permission from [41,53,54]. (C) Lysosome-targeted C-TiO2/CDs@FA-/RuNO-Lyso nanomedicine. Reproduced with permission from [55]. (D) Mitochondrion-targeted RuNO-N-GQD-TPP (left) and SNO-Cdot-TPP (right) nanomedicines. Reproduced with permission from [56] and [57]. (E) Magnet-targeted Fe2O3-ADT@DPPC-DSPE-PEG2K nanomedicine. Reproduced with permission from [58].
Figure 9.
Figure 9.
Schematic illustration of target points of various cancer therapy methods.
Figure 10.
Figure 10.
Representative multimodal combination therapy strategies based on gas-releasing nanomedicines. (A) The DOX-RBS-UCNP@MSN (left) and DOX-CaCO3 (right) nanomedicines for gasochemotherapy. Reproduced with permission from [62] and [60]. (B) The SNO@UCNP-MSN (above) and O2-PFC@Bi2Se3-PEG (below) nanomedicines for gasoradiotherapy. Reproduced with permission from [10] and [63]. (C) The PdH0.2 (left) and FeCO-mPB-PEG (right) nanomedicines for gasophotothermal therapy. Reproduced with permission from [26] and [64]. (D) The FeCO-MnO2@MSN nanomedicine for gasochemodynamic therapy. Reproduced with permission from [65]. (E) The HSA-Ce6@MnO2 nanomedicine for gasophotodynamic therapy. Reproduced with permission from [66]. (F) The TPZ@HMTN-SNO (left) and HMME@MCC-HA (right) nanomedicines. Reproduced with permission from [67] and [68].
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