Nanotherapeutics for the Treatment of Hepatocellular Carcinoma

Aptamers and Their Potential in Site-Specific Nanotherapy Against Hepatocellular Carcinoma

Author(s): Debasmita Dutta*, Samrat Chakraborty, Biswajit Mukherjee, Moumita Dhara and Laboni Das

Pp: 280-315 (36)

DOI: 10.2174/9789815039740122010009

* (Excluding Mailing and Handling)

Abstract

Globally, hepatocellular carcinoma (HCC) is one of the most devastating
neoplasia and has a remarkably high mortality rate. Furthermore, the long latent period
associated with HCC lends the diagnosis at the intermediate or advanced stages where
the chemotherapy is the solitary therapeutic intervention. The responsiveness of HCC
towards conventional chemotherapeutic agents is notably poor due to multiple factors.
Among them, multiple drug resistance, reduced drug concentration at the tumor site,
quicker clearance, and non-specific distribution are the prime causes leading to
remarkably high off-target toxicity and mortality. More importantly, the approval of
several multikinase inhibitors (MKIs) by the United States Food and Drug
Administration (FDA) for the treatment of HCC as targeted therapeutics has been
found to be inadequate to make a notable impact on survival. Therefore, ligand-based
targeted therapeutics capable of delivering the therapeutic modality specifically into
neoplastic hepatocytes have been explored extensively by researchers worldwide.
Among the plethora of HCC-targeting ligands, aptamer-based targeted therapeutics in
HCC have gained significant momentum compared to others due to some signature
characteristics of aptamer, namely non-immunogenicity, low cost, non-toxicity,
thermostability, simpler manufacturing, and high suitability for chemical modification.
Despite their enormous potential, aptamer-based targeted therapeutics are still in
infancy and require smarter thinking and quick translation from e-clinical to clinical
application. Thus, the fundamental focus of the book chapter is to highlight promising
features of aptamers, their production, chemical modification, mechanism of action,
and finally, detailed emphasis has been given on the overall scenario of aptamer-based
targeted therapeutics in HCC.


Keywords: Aptamers, Diagnosis, Hepatocellular carcinoma, Nanoencapsulated drug delivery, Targeted therapy, Theranostic treatment.

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      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1518
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59228343 and j.to_ip >=59228343 )) and ((j.from_date <= 1739988346 and j.to_date >= 1739988346 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 16546) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59228343 and j.to_ip >=59228343 )) and ((j.from_date <= 1739988346 and j.to_date >= 1739988346 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 16546) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59228343 and j.to_ip >=59228343 )) and ((j.from_date <= 1739988346 and j.to_date >= 1739988346 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 16546)
      580μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1549
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` where `b`.`banner_ebook` = 1 and `bd`.`content_type` = 'B' and `bd`.`content_id` = 3312 and `b`.`banner_from_date` <= 1739988346 and `b`.`banner_to_date` >= 1739988346 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.1msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: B
      • 2: 3312
      • 3: 1739988346
      • 4: 1739988346
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select count(*) as aggregate from `uc_cart_products` where cart_id='d3b7a68916b1528e41493d9dd964f328'
      250μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:260
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    App\Models\Keywords
    6Keywords.php#?
    App\Models\Chapter
    1Chapter.php#?
    App\Models\Ebook
    1Ebook.php#?
        _token
        q4aX3QXELGvU2mOhnqgGih72WtwpRZPDEgSBo8XG
        uc_cart_id
        d3b7a68916b1528e41493d9dd964f328
        _previous
        array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/16546" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /chapter/16546
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
        array:17 [ "x-https" => array:1 [ 0 => "1" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] "priority" => array:1 [ 0 => "u=0, i" ] "cookie" => array:1 [ 0 => "wayfindertarget=eyJpdiI6ImJ5blQ2b1BKWkFlNksvRnpFdkFiZ3c9PSIsInZhbHVlIjoib2VZL0RpZEF4WGRHMEU3T1lJRHdJaDdueXBsbWt6TzF6TzNmVE5idVdHcz0iLCJtYWMiOiIwY2VhMDhkOTYwNzFhMTRmM2ZhMTQxZDk3N2UwYWI1N2EzMTExZTlkYjE2NGQ0MGYyZGFkNjkwYzg1NzI5NDgxIiwidGFnIjoiIn0%3Dwayfindertarget=eyJpdiI6ImJ5blQ2b1BKWkFlNksvRnpFdkFiZ3c9PSIsInZhbHVlIjoib2VZL0RpZEF4WGRHMEU3T1lJRHdJaDdueXBsbWt6TzF6TzNmVE5idVdHcz0iLCJtYWMiOiIwY2VhMDhkOTYwNzFh" ] "accept-encoding" => array:1 [ 0 => "gzip, deflate, br, zstd" ] "sec-fetch-dest" => array:1 [ 0 => "document" ] "sec-fetch-user" => array:1 [ 0 => "?1" ] "sec-fetch-mode" => array:1 [ 0 => "navigate" ] "sec-fetch-site" => array:1 [ 0 => "none" ] "accept" => array:1 [ 0 => "text/html,application/xhtml+xml,application/xml;q=0.9,image/avif,image/webp,image/apng,*/*;q=0.8,application/signed-exchange;v=b3;q=0.7" ] "user-agent" => array:1 [ 0 => "Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)" ] "upgrade-insecure-requests" => array:1 [ 0 => "1" ] "sec-ch-ua-platform" => array:1 [ 0 => ""Windows"" ] "sec-ch-ua-mobile" => array:1 [ 0 => "?0" ] "sec-ch-ua" => array:1 [ 0 => ""HeadlessChrome";v="129", "Not=A?Brand";v="8", "Chromium";v="129"" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] ]
        request_cookies
        0 of 0
        array:1 [ "wayfindertarget" => null ]
        response_headers
        0 of 0
        array:5 [ "content-type" => array:1 [ 0 => "text/html; charset=UTF-8" ] "cache-control" => array:1 [ 0 => "no-cache, private" ] "date" => array:1 [ 0 => "Wed, 19 Feb 2025 18:05:46 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IjRXWmJlMC9hWGZDZTFDU0NsMmcwSVE9PSIsInZhbHVlIjoiaTY3L2ZZWHAydlVOaTRPNTJtNi9kNkh4T2RIRmt4dGJBZ1k0TE1uUFo4bXVHUmcrUGw3V3Fzdktwc1UzTVdTdXRQQUNieUV6Y0ExeHZpeUNHcTdIWDRGTVNOaGpZbWM4VTRtV2xTSjdXTlJROE55QmdjL0JBNUd2T1ZMamZhRlEiLCJtYWMiOiI1Zjg3NWRmNTg3ZTQ2OTI4ZmU0NDU2YzZmYmVjMGMwYzMyYmMxNTRiY2VlMmExNjFkOWI4ODAyMjczNWJlNTk2IiwidGFnIjoiIn0%3D; expires=Sat, 22 Feb 2025 06:05:46 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6IjRXWmJlMC9hWGZDZTFDU0NsMmcwSVE9PSIsInZhbHVlIjoiaTY3L2ZZWHAydlVOaTRPNTJtNi9kNkh4T2RIRmt4dGJBZ1k0TE1uUFo4bXVHUmcrUGw3V3Fzdktwc1UzTVdTdXRQQUNie" 1 => "alphaeurekaselectnet_session=eyJpdiI6ImxCTTQyZFpGQi9OYkw4MjlDRHJPL3c9PSIsInZhbHVlIjoidC8vL3VReVJSVVVINjBBS2lOU2plQTA3ZkJlYUNKRXZhSDA3YTVFZGxnSE5vWTQyZjl4dlBuMFpjaU4vd1FZVEJORzJGVE54QTRHb09rM0tiaWZFdEVEd1pxdFFDejJEVjAwNmIwUWcrZFV6K2xmM2R3Z0l2ZnBBNEt1NWxTTDQiLCJtYWMiOiJhNzgzZTQ0MTMyODY1OTAzNWQ3YWE0NTJlMWYwZWZlMDcyNWRkZmRlNzk3Y2RiMzYxOTAzMDI0MjBhYmVmM2YzIiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6ImxCTTQyZFpGQi9OYkw4MjlDRHJPL3c9PSIsInZhbHVlIjoidC8vL3VReVJSVVVINjBBS2lOU2plQTA3ZkJlYUNKRXZhSDA3YTVFZGxnSE5vWTQyZjl4dlBuMFp" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IjRXWmJlMC9hWGZDZTFDU0NsMmcwSVE9PSIsInZhbHVlIjoiaTY3L2ZZWHAydlVOaTRPNTJtNi9kNkh4T2RIRmt4dGJBZ1k0TE1uUFo4bXVHUmcrUGw3V3Fzdktwc1UzTVdTdXRQQUNieUV6Y0ExeHZpeUNHcTdIWDRGTVNOaGpZbWM4VTRtV2xTSjdXTlJROE55QmdjL0JBNUd2T1ZMamZhRlEiLCJtYWMiOiI1Zjg3NWRmNTg3ZTQ2OTI4ZmU0NDU2YzZmYmVjMGMwYzMyYmMxNTRiY2VlMmExNjFkOWI4ODAyMjczNWJlNTk2IiwidGFnIjoiIn0%3D; expires=Sat, 22-Feb-2025 06:05:46 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6IjRXWmJlMC9hWGZDZTFDU0NsMmcwSVE9PSIsInZhbHVlIjoiaTY3L2ZZWHAydlVOaTRPNTJtNi9kNkh4T2RIRmt4dGJBZ1k0TE1uUFo4bXVHUmcrUGw3V3Fzdktwc1UzTVdTdXRQQUNie" 1 => "alphaeurekaselectnet_session=eyJpdiI6ImxCTTQyZFpGQi9OYkw4MjlDRHJPL3c9PSIsInZhbHVlIjoidC8vL3VReVJSVVVINjBBS2lOU2plQTA3ZkJlYUNKRXZhSDA3YTVFZGxnSE5vWTQyZjl4dlBuMFpjaU4vd1FZVEJORzJGVE54QTRHb09rM0tiaWZFdEVEd1pxdFFDejJEVjAwNmIwUWcrZFV6K2xmM2R3Z0l2ZnBBNEt1NWxTTDQiLCJtYWMiOiJhNzgzZTQ0MTMyODY1OTAzNWQ3YWE0NTJlMWYwZWZlMDcyNWRkZmRlNzk3Y2RiMzYxOTAzMDI0MjBhYmVmM2YzIiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6ImxCTTQyZFpGQi9OYkw4MjlDRHJPL3c9PSIsInZhbHVlIjoidC8vL3VReVJSVVVINjBBS2lOU2plQTA3ZkJlYUNKRXZhSDA3YTVFZGxnSE5vWTQyZjl4dlBuMFp" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "q4aX3QXELGvU2mOhnqgGih72WtwpRZPDEgSBo8XG" "uc_cart_id" => "d3b7a68916b1528e41493d9dd964f328" "_previous" => array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/16546" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-19 18:05:46GET/chapter/16546112198